Browsing by Author "Kumar, Adarsh"

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    Applications of dihydropyrimidinone derivatives on blood cancer and colon cancer
    (Elsevier, 2023-08-25T00:00:00) Singh, Ankit Kumar; Singh, Harshwardhan; Sonawane, Pankaj; Kumar, Adarsh; Verma, Amita; Kumar, Pradeep
    Dihydropyrimidinones (DHPMs) are characterized by their multifunctionalized scaffold with a pyrimidine moiety that exhibits diverse biological activities, especially anticancer activity. Malignant clonal expansion of blood-forming cells is referred to as blood cancer. Colorectal cancer (CRC) appears within the colon or another bodily area. There were 9,958,133 fatalities and 19,292,789 new cases of 36 cancers globally in 2020. In this, 1,148,515 cases and 576,858 deaths belong to colon cancer, whereas 474,519 cases and 311,594 deaths belong to leukemia. Different blood cancer cell lines, such as MOLT-4, HL-60, CCRF-CEMT, K-562, U937, MOLT-4, RPMI-8226, THP-1, and SR, as well as colon cancer/CRC cell lines, HCT-116, HCT-15, Colo205, HCC-2998, HCT-116, HT-29, KM-12, and SW-620, have been used to evaluate in vitro anticancer activity of DHPM derivatives. DHPM derivatives demonstrated notable effectiveness against blood and colon/colorectal cancers and may prove important building blocks in the development of novel anticancer agents. � 2023 Elsevier Inc. All rights reserved.
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    Bacteriophages Concept and Applications: A Review on Phage Therapy
    (Bentham Science Publishers, 2022-11-07T00:00:00) Sahu, Rasti; Singh, Ankit Kumar; Kumar, Adarsh; Singh, Kuldeep; Kumar, Pradeep
    The nature of phages was a matter of dispute, which was resolved in 1940, and it was continued to develop their activity and application in the Soviet Union and Eastern Europe. Bacterio-phages were first employed in 1919 to treat bacterial illnesses caused by Citrobacter, Enterobacter, and Pseudomonas. Bacteriophages range in complexity from simple spherical viruses with genome sizes of less than 5 kbp to complicated viruses with genome sizes surpassing 280 kbp. They have two significant parts, head and tail, and are made up of numerous copies of more than 40 distinct proteins. Bacteriophages have been demonstrated to bind with receptors in the walls of both gram-positive and gram-negative bacteria, ranging from peptide sequences to polysaccharide moieties. Depending on the type of phage and the physiological state of the bacterium, the life cycle may diverge into the lytic cycle or lysogenic cycle. Lytic-lysogenic switch depends on a variety of inducing factors. Bacteriophage therapy can be administered via several routes, but parenteral routes are the most effec-tive. Auto-dosing, single-dose potential, lack of cross-resistance with antibiotics, etc., are several advantages of phage therapy over antibiotic treatment. Bacteriophages are attracting much attention because of their potential advantages and wide applications as antibacterial agents, diagnostic technolo-gies, phage-based products, and biocontrol agents. They also have several applications in the food industry, agriculture/crop, farm animal and bee protection, environmental, and biosensor development. � 2023 Bentham Science Publishers.
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    Biotechnological attributes of biostimulants for relieving metal toxicity
    (Elsevier, 2023-08-04T00:00:00) Rana, Varnika; Kumar, Adarsh; Singh, Reetu; Kumar, Vinay
    A global scourge, heavy metals (HMs) toxicity with high concentration causes reactive oxygen species (ROS) to attack key biological molecules and has emerged in the past few years, posing a serious threat to human lives and ecosystems and agriculture. In plants, HMs alter the genome and genetic structure and eventually affect their protein and enzyme activities which further impede cellular metabolism. Therefore the growing body of scientific research is emphasizing green synthesis, that is, biostimulants use as the nexus of biotechnology and fertilizer that can be viewed as novel, efficient, eco-friendly, and cost-effective tools to safeguard the detrimental effects on ecosystems. In this regard, this chapter aims to scrutinize the role of various biostimulants against abiotic stresses using various biostimulants including seaweed extracts, protein hydrolysates, humic acids, and fulvic acids. The microbial-based stimulants are also discussed in this chapter. A list of biological processes has also been highlighted as prime targets for removing heavy metal(loid)s toxicity using biotechnological interventions. The biostimulants enhance growth and improve stress tolerance ability in plants. A table of targeted biotechnological attributes is also provided. Recently, a steep rise in interest in biostimulants is driving the development of sustainable green economics and agricultural concepts, while increasing demand for new products and understanding their mechanism of action is increasing. Further, the increasing demand for innovative biostimulants products and an interest in understanding their mechanisms of action will drive HM-free green economics and agricultural sustainability in the coming days. � 2023 Elsevier Inc. All rights reserved.
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    Biotechnological attributes of biostimulants for relieving metal toxicity
    (Elsevier, 2023-08-04T00:00:00) Rana, Varnika; Kumar, Adarsh; Singh, Reetu; Kumar, Vinay
    A global scourge, heavy metals (HMs) toxicity with high concentration causes reactive oxygen species (ROS) to attack key biological molecules and has emerged in the past few years, posing a serious threat to human lives and ecosystems and agriculture. In plants, HMs alter the genome and genetic structure and eventually affect their protein and enzyme activities which further impede cellular metabolism. Therefore the growing body of scientific research is emphasizing green synthesis, that is, biostimulants use as the nexus of biotechnology and fertilizer that can be viewed as novel, efficient, eco-friendly, and cost-effective tools to safeguard the detrimental effects on ecosystems. In this regard, this chapter aims to scrutinize the role of various biostimulants against abiotic stresses using various biostimulants including seaweed extracts, protein hydrolysates, humic acids, and fulvic acids. The microbial-based stimulants are also discussed in this chapter. A list of biological processes has also been highlighted as prime targets for removing heavy metal(loid)s toxicity using biotechnological interventions. The biostimulants enhance growth and improve stress tolerance ability in plants. A table of targeted biotechnological attributes is also provided. Recently, a steep rise in interest in biostimulants is driving the development of sustainable green economics and agricultural concepts, while increasing demand for new products and understanding their mechanism of action is increasing. Further, the increasing demand for innovative biostimulants products and an interest in understanding their mechanisms of action will drive HM-free green economics and agricultural sustainability in the coming days. � 2023 Elsevier Inc. All rights reserved.
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    Challenges and Opportunities in the Crusade of BRAF Inhibitors: From 2002 to 2022
    (American Chemical Society, 2023-07-26T00:00:00) Singh, Ankit Kumar; Sonawane, Pankaj; Kumar, Adarsh; Singh, Harshwardhan; Naumovich, Vladislav; Pathak, Prateek; Grishina, Maria; Khalilullah, Habibullah; Jaremko, Mariusz; Emwas, Abdul-Hamid; Verma, Amita; Kumar, Pradeep
    Serine/threonine-protein kinase B-Raf (BRAF; RAF = rapidly accelerated fibrosarcoma) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade. Somatic mutations in the BRAF gene were first discovered in 2002 by Davies et al., which was a major breakthrough in cancer research. Subsequently, three different classes of BRAF mutants have been discovered. This class includes class I monomeric mutants (BRAFV600), class II BRAF homodimer mutants (non-V600), and class III BRAF heterodimers (non-V600). Cancers caused by these include melanoma, thyroid cancer, ovarian cancer, colorectal cancer, nonsmall cell lung cancer, and others. In this study, we have highlighted the major binding pockets in BRAF protein, their active and inactive conformations with inhibitors, and BRAF dimerization and its importance in paradoxical activation and BRAF mutation. We have discussed the first-, second-, and third-generation drugs approved by the Food and Drug Administration and drugs under clinical trials with all four different binding approaches with DFG-IN/OUT and ?C-IN/OUT for BRAF protein. We have investigated particular aspects and difficulties with all three generations of inhibitors. Finally, this study has also covered recent developments in synthetic BRAF inhibitors (from their discovery in 2002 to 2022), their unique properties, and importance in inhibiting BRAF mutants. � 2023 The Authors. Published by American Chemical Society.
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    Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids
    (MDPI, 2022-08-30T00:00:00) Singh, Ankit Kumar; Kumar, Adarsh; Singh, Harshwardhan; Sonawane, Pankaj; Paliwal, Harshali; Thareja, Suresh; Pathak, Prateek; Grishina, Maria; Jaremko, Mariusz; Emwas, Abdul-Hamid; Yadav, Jagat Pal; Verma, Amita; Khalilullah, Habibullah; Kumar, Pradeep
    Cancer is a complex disease, and its treatment is a big challenge, with variable efficacy of conventional anticancer drugs. A two-drug cocktail hybrid approach is a potential strategy in recent drug discovery that involves the combination of two drug pharmacophores into a single molecule. The hybrid molecule acts through distinct modes of action on several targets at a given time with more efficacy and less susceptibility to resistance. Thus, there is a huge scope for using hybrid compounds to tackle the present difficulties in cancer medicine. Recent work has applied this technique to uncover some interesting molecules with substantial anticancer properties. In this study, we report data on numerous promising hybrid anti-proliferative/anti-tumor agents developed over the previous 10 years (2011�2021). It includes quinazoline, indole, carbazole, pyrimidine, quinoline, quinone, imidazole, selenium, platinum, hydroxamic acid, ferrocene, curcumin, triazole, benzimidazole, isatin, pyrrolo benzodiazepine (PBD), chalcone, coumarin, nitrogen mustard, pyrazole, and pyridine-based anticancer hybrids produced via molecular hybridization techniques. Overall, this review offers a clear indication of the potential benefits of merging pharmacophoric subunits from multiple different known chemical prototypes to produce more potent and precise hybrid compounds. This provides valuable knowledge for researchers working on complex diseases such as cancer. � 2022 by the authors.
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    Current insights and molecular docking studies of HIV-1 reverse transcriptase inhibitors
    (John Wiley and Sons Inc, 2023-10-12T00:00:00) Singh, Ankit Kumar; Kumar, Adarsh; Arora, Sahil; Kumar, Raj; Verma, Amita; Khalilullah, Habibullah; Jaremko, Mariusz; Emwas, Abdul-Hamid; Kumar, Pradeep
    Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide were living with HIV in 2021. Viral reverse transcriptase (RT) is an excellent target for drug intervention. Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of approved antiretroviral drugs. Later, a new type of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were approved as anti-HIV drugs. Zidovudine, didanosine, and stavudine are FDA-approved NRTIs, while nevirapine, efavirenz, and delavirdine are FDA-approved NNRTIs. Several agents are in clinical trials, including apricitabine, racivir, elvucitabine, doravirine, dapivirine, and elsulfavirine. This review addresses HIV-1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA-approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART). � 2023 John Wiley & Sons Ltd.
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    Current Insights and Molecular Docking Studies of the Drugs under Clinical Trial as RdRp Inhibitors in COVID-19 Treatment
    (Bentham Science Publishers, 2022-11-08T00:00:00) Pauly, Irine; Singh, Ankit Kumar; Kumar, Adarsh; Singh, Yogesh; Thareja, Suresh; Kamal, Mohammad A.; Verma, Amita; Kumar, Pradeep
    Study Background & Objective: After the influenza pandemic (1918), COVID-19 was declared a Vth pandemic by the WHO in 2020. SARS-CoV-2 is an RNA-enveloped single-stranded virus. Based on the structure and life cycle, Protease (3CLpro), RdRp, ACE2, IL-6, and TMPRSS2 are the major targets for drug development against COVID-19. Pre-existing several drugs (FDA-approved) are used to inhibit the above targets in different diseases. In coronavirus treatment, these drugs are also in different clinical trial stages. Remdesivir (RdRp inhibitor) is the only FDA-approved medicine for coronavirus treatment. In the present study, by using the drug repurposing strategy, 70 preexisting clinical or under clinical trial molecules were used in scrutiny for RdRp inhibitor potent molecules in coronavirus treatment being surveyed via docking studies. Molecular simulation studies further confirmed the binding mechanism and stability of the most potent compounds. Material and Methods: Docking studies were performed using the Maestro 12.9 module of Schrodinger soft-ware over 70 molecules with RdRp as the target and remdesivir as the standard drug and further confirmed by simulation studies. Results: The docking studies showed that many HIV protease inhibitors demonstrated remarkable binding interactions with the target RdRp. Protease inhibitors such as lopinavir and ritonavir are effective. Along with these, AT-527, ledipasvir, bicalutamide, and cobicistat showed improved docking scores. RMSD and RMSF were further analyzed for potent ledipasvir and ritonavir by simulation studies and were identified as potential candidates for corona disease. Conclusion: The drug repurposing approach provides a new avenue in COVID-19 treatment. � 2022 Bentham Science Publishers.
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    Current Insights into the Role of BRAF Inhibitors in Treatment of Melanoma
    (Bentham Science Publishers, 2022-06-28T00:00:00) Singh, Ankit Kumar; Kumar, Adarsh; Thareja, Suresh; Kumar, Pradeep
    Melanomas represent only 4% of all skin cancers, but their mortality rate is more than 50 % of any other skin cancer. Alteration in genetic and environmental factors are the risk factors for melanoma development. The RAS/RAF/MEK/ERK or Mitogen-activated protein kinase (MAPK) pathway is activated in melanoma. BRAF activation is necessary to govern differentiation, proliferation, and survival. Mutations in BRAF were found in 80�90% of all melanomas. Over 90% of BRAF mutations occur at codon 600, and over 90% of them are BRAFV600E other common mutations are BRAFV600K, BRAFV600R, BRAF V600?E2?, and BRAF V600D. Based on ?C-helix and DFG motif (?C-helix-IN/DFG-IN), (?C-helix-IN/DFG-OUT), (?C-helix-OUT/DFG-IN) and (?C-helix-OUT/ DFG-OUT) are four structural types of inhibitors for targeting BRAF. Sorafenib, Vemurafenib, Dabrafenib, and Encorafenib are FDA-approved for the treatment of BRAF. Understanding melanoma pathogenesis, RAS/RAF/MEK/ERK or MAPK path-way, and BRAF conformations, mutations, the problems with FDA approved BRAF inhibitors will be important for new drug discovery, modification of existing BRAF barriers to improve target specific action, and prevent increasing response levels while minimizing toxicity. � 2023 Bentham Science Publishers.
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    Design, one-pot synthesis, computational and biological evaluation of diaryl benzimidazole derivatives as MEK inhibitors
    (Taylor and Francis Ltd., 2023-10-09T00:00:00) Ram, Teja; Singh, Ankit Kumar; Pathak, Prateek; Kumar, Adarsh; Singh, Harshwardhan; Grishina, Maria; Novak, Jurica; Kumar, Pradeep
    MEK mutations are more common in various human malignancies, such as pancreatic cancer (70�90%), mock melanoma (50%), liver cancer (20�40%), colorectal cancer (25�35%), melanoma (15�20%), non-small cell lung cancer (10�20%) and basal breast cancer (1�5%). Considering the significance of MEK mutations in diverse cancer types, the rational design of the proposed compounds relies on the structural resemblance to FDA-approved MEK inhibitors like selumetinib and binimetinib. The compound under design features distinct substitutions at the benzimidazole moiety, specifically at positions 2 and 3, akin to the FDA-approved drugs, albeit differing in positions 5 and 6. Subsequent structural refinement was guided by key elements including the DFG motif, hydrophobic pocket and catalytic loop of the MEK protein. A set of 15 diverse diaryl benzimidazole derivatives (S1�S15) were synthesized via a one-pot approach and characterized through spectroscopic techniques, including MASS, IR, 1H NMR and 13C NMR. In vitro anticancer activities of all the synthesized compounds were evaluated against four cancer cell lines, A375, HT ?29, A431 and HFF, along with the standard drug trametinib. Molecular docking was performed for all synthesized compounds (S1�15), followed by 950 ns molecular dynamics simulation studies for the promising compounds S1, S5 and S15. The stability of these complexes was assessed by calculating the root-mean-square deviation, solvent accessible surface area and gyration radius relative to their parent structures. Additionally, free energy of binding calculations were performed. Based on the biological and computational results, S15 was the most potent compound and S1 and S5 are comparable to the standard drug trametinib. Communicated by Ramaswamy H. Sarma. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
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    Dihydropyrimidinone scaffold and potential therapeutic targets
    (Elsevier, 2023-08-25T00:00:00) Kumar, Adarsh; Singh, Ankit Kumar; Vijayan, Veena; Singh, Harshwardhan; Verma, Amita; Kumar, Pradeep
    Dihydropyrimidine is the most important heterocyclic ring system involved in the synthesis of RNA and DNA. Dihydropyrimidines were produced synthetically by multicomponent reactions such as the Biginelli reaction. Because of their remarkable biological characteristics, dihydropyrimidinones (DHPMs) have drawn considerable attention in recent years. In this chapter, we have described the synthetic and pharmacological properties of DHPMs employing multicomponent synthesis. It emphasizes also widespread pharmaceutical applications of DHPMs, including antitubercular, antifilarial, antihypertensive, antiinflammatory, anticancer, antifungal, antibacterial, anti-HIV, antihyperglycemic, anti-SARS, analgesic, antioxidant, anticonvulsant, anti-Alzheimer�s and antihepatitis properties. This chapter will be of immense importance for the scientists working in this area. � 2023 Elsevier Inc. All rights reserved.
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    Gaussian field-based 3D-QSAR and molecular simulation studies to design potent pyrimidine-sulfonamide hybrids as selective BRAFV600E inhibitors
    (Royal Society of Chemistry, 2022-10-21T00:00:00) Singh, Ankit Kumar; Novak, Jurica; Kumar, Adarsh; Singh, Harshwardhan; Thareja, Suresh; Pathak, Prateek; Grishina, Maria; Verma, Amita; Yadav, Jagat Pal; Khalilullah, Habibullah; Pathania, Vikas; Nandanwar, Hemraj; Jaremko, Mariusz; Emwas, Abdul-Hamid; Kumar, Pradeep
    The �RAS-RAF-MEK-ERK� pathway is an important signaling pathway in melanoma. BRAFV600E (70-90%) is the most common mutation in this pathway. BRAF inhibitors have four types of conformers: type I (?C-IN/DFG-IN), type II (?C-IN/DFG-OUT), type I1/2 (?C-OUT/DFG-IN), and type I/II (?C-OUT/DFG-OUT). First- and second-generation BRAF inhibitors show resistance to BRAFV600E and are ineffective against malignancies induced by dimer BRAF mutants causing �paradoxical� activation. In the present study, we performed molecular modeling of pyrimidine-sulfonamide hybrids inhibitors using 3D-QSAR, molecular docking, and molecular dynamics simulations. Previous reports reveal the importance of pyrimidine and sulfonamide moieties in the development of BRAFV600E inhibitors. Analysis of 3D-QSAR models provided novel pyrimidine sulfonamide hybrid BRAFV600E inhibitors. The designed compounds share similarities with several structural moieties present in first- and second-generation BRAF inhibitors. A total library of 88 designed compounds was generated and molecular docking studies were performed with them. Four molecules (T109, T183, T160, and T126) were identified as hits and selected for detailed studies. Molecular dynamics simulations were performed at 900 ns and binding was calculated. Based on molecular docking and simulation studies, it was found that the designed compounds have better interactions with the core active site [the nucleotide (ADP or ATP) binding site, DFG motif, and the phospho-acceptor site (activation segment) of BRAFV600E protein than previous inhibitors. Similar to the FDA-approved BRAFV600E inhibitors the developed compounds have [?C-OUT/DFG-IN] conformation. Compounds T126, T160 and T183 interacted with DIF (Leu505), making them potentially useful against BRAFV600E resistance and malignancies induced by dimer BRAF mutants. The synthesis and biological evaluation of the designed molecules is in progress, which may lead to some potent BRAFV600E selective inhibitors. � 2022 The Royal Society of Chemistry.
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    Genetically modified crop regulations: scope and opportunity using the CRISPR-Cas9 genome editing approach
    (Springer Science and Business Media B.V., 2021-06-10T00:00:00) Gupta, Shweta; Kumar, Adarsh; Patel, Rupali; Kumar, Vinay
    Global demand for food is increasing day by day due to an increase in population and shrinkage of the arable land area. To meet this increasing demand, there is a need to develop high-yielding varieties that are nutritionally enriched and tolerant against environmental stresses. Various techniques are developed for improving crop quality such as mutagenesis, intergeneric crosses, and translocation breeding. Later, with the development of genetic engineering, genetically modified crops came up with the transgene insertion approach which helps to withstand adverse conditions. The process or product-focused approaches are used for regulating genetically modified crops with their risk analysis on the environment and public health. However, recent advances in gene-editing technologies have led to a new era of plant breeding by developing techniques including site-directed nucleases, zinc finger nucleases, and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) that involve precise gene editing without the transfer of foreign genes. But these techniques always remain in debate for their regulation status and public acceptance. The European countries and New Zealand, consider the gene-edited plants under the category of genetically modified organism (GMO) regulation while the USA frees the gene-edited plants from such type of regulations. Considering them under the category of GMO makes a long and complicated approval process to use them, which would decrease their immediate commercial value. There is a need to develop strong regulatory approaches for emerging technologies that expedite crop research and attract people to adopt these new varieties without hesitation. � 2021, The Author(s), under exclusive licence to Springer Nature B.V.
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    Genetically modified crop regulations: scope and opportunity using the CRISPR-Cas9 genome editing approach
    (Springer Science and Business Media B.V., 2021-06-10T00:00:00) Gupta, Shweta; Kumar, Adarsh; Patel, Rupali; Kumar, Vinay
    Global demand for food is increasing day by day due to an increase in population and shrinkage of the arable land area. To meet this increasing demand, there is a need to develop high-yielding varieties that are nutritionally enriched and tolerant against environmental stresses. Various techniques are developed for improving crop quality such as mutagenesis, intergeneric crosses, and translocation breeding. Later, with the development of genetic engineering, genetically modified crops came up with the transgene insertion approach which helps to withstand adverse conditions. The process or product-focused approaches are used for regulating genetically modified crops with their risk analysis on the environment and public health. However, recent advances in gene-editing technologies have led to a new era of plant breeding by developing techniques including site-directed nucleases, zinc finger nucleases, and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) that involve precise gene editing without the transfer of foreign genes. But these techniques always remain in debate for their regulation status and public acceptance. The European countries and New Zealand, consider the gene-edited plants under the category of genetically modified organism (GMO) regulation while the USA frees the gene-edited plants from such type of regulations. Considering them under the category of GMO makes a long and complicated approval process to use them, which would decrease their immediate commercial value. There is a need to develop strong regulatory approaches for emerging technologies that expedite crop research and attract people to adopt these new varieties without hesitation. � 2021, The Author(s), under exclusive licence to Springer Nature B.V.
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    In Silico Studies of Indole Derivatives as Antibacterial Agents
    (Korean Pharmacopuncture Institute, 2023-06-30T00:00:00) Shah, Mridul; Kumar, Adarsh; Singh, Ankit Kumar; Singh, Harshwardhan; Narasimhan, Balasubramanian; Kumar, Pradeep
    Objectives: Molecular docking and QSAR studies of indole derivatives as antibacterial agents. Methods: In this study, we used a multiple linear regressions (MLR) approach to construct a 2D quantitative structure activity relationship of 14 reported indole derivatives. It was performed on the reported antibacterial activity data of 14 compounds based on theoretical chemical descriptors to construct statistical models that link structural properties of indole derivatives to antibacterial activity. We have also performed molecular docking studies of same compounds by using Maestro module of Schrodinger. A set the molecular descriptors like hydrophobic, geometric, electronic and topological characters were calculated to represent the structural features of compounds. The conventional antibiotics sultamicillin and ampicillin were not used in the model development since their structures are different from those of the created compounds. Biological activity data was first translated into pMIC values (i.e. -log MIC) and used as a dependent variable in QSAR investigation. Results: Compounds with high electronic energy and dipole moment were effective antibacterial agents against S. aureus, indole derivatives with lower ?2 values were excellent antibacterial agents against MRSA standard strain, and compounds with lower R value and a high 2?v value were effective antibacterial agents against MRSA isolate. Conclusion: Compounds 12 and 2 showed better binding score against penicillin binding protein 2 and penicillin binding protein 2a respectively. Copyright � Korean Pharmacopuncture Institute
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    An Insight to Heat Shock Protein 90: A Remedy for Multiple Problems
    (Bentham Science Publishers, 2022-08-30T00:00:00) Yadav, Megha; Singh, Ankit Kumar; Kumar, Adarsh; Thareja, Suresh; Kumar, Pradeep
    Heat shock protein 90 (Hsp90) is a chaperone protein that prevents many other proteins from aggre-gating by folding them in a certain way. Hsp90 consists of three structural domains: N-terminal, middle and C-terminal domains. Hsp90 has many activities in numerous proteins and signaling pathways like chimeric fusion proteins, steroid hormone receptors, tumor suppressor genes, and cell cycle regulatory proteins. The role of Hsp90 is not only in cancer but also in other diseases like COVID-19, leishmaniasis, diabetes, flavi virus, systemic sclerosis, grass carp reovirus, psoriasis, malaria, cardiac fibrosis, and alcohol-related liver diseases. This review is a compilation of the pharmacological profile of Hsp90 inhibitors, problems associated with them, and suggested remedies for the same. � 2022 Bentham Science Publishers.
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    Medicinal Chemistry Aspects of Isoxazole Analogues as Anti-tubercular Agents
    (Bentham Science Publishers, 2023-10-11T00:00:00) Singh, Harshwardhan; Anila, Kumari V. S.; Singh, Ankit Kumar; Kumar, Adarsh; Kumar, Pradeep
    Tuberculosis (TB) is the major cause of mortality around the world and one of the most common diseases linked to AIDS. Due to the emergence of multi-drug resistance, extensive drug resistance, and total drug resistance strains, TB has become a difficult disease to treat. Isoxazole scaffold shows a wide range of biological activities, including anticancer, antibacterial, anti-tubercular, antiviral, and anti-inflammatory activities etc. Several isoxazole derivatives have been produced and few of them have shown comparable anti-tubercular activity with standard drugs. In this review, we have focused on reported isoxazole derivatives having anti-tubercular activity and summarized their structure-activity relationship. � 2023 Bentham Science Publishers.
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    Medicinal chemistry perspective of pyrido[2,3-d]pyrimidines as anticancer agents
    (Royal Society of Chemistry, 2023-03-03T00:00:00) Kumar, Adarsh; Bhagat, Kuber Kumar; Singh, Ankit Kumar; Singh, Harshwardhan; Angre, Tanuja; Verma, Amita; Khalilullah, Habibullah; Jaremko, Mariusz; Emwas, Abdul-Hamid; Kumar, Pradeep
    Cancer is a major cause of deaths across the globe due to chemoresistance and lack of selective chemotherapy. Pyrido[2,3-d]pyrimidine is an emerging scaffold in medicinal chemistry having a broad spectrum of activities, including antitumor, antibacterial, CNS depressive, anticonvulsant, and antipyretic activities. In this study, we have covered different cancer targets, including tyrosine kinase, extracellular regulated protein kinases - ABL kinase, phosphatidylinositol-3 kinase, mammalian target of rapamycin, p38 mitogen-activated protein kinases, BCR-ABL, dihydrofolate reductase, cyclin-dependent kinase, phosphodiesterase, KRAS and fibroblast growth factor receptors, their signaling pathways, mechanism of action and structure-activity relationship of pyrido[2,3-d]pyrimidine derivatives as inhibitors of the above-mentioned targets. This review will represent the complete medicinal and pharmacological profile of pyrido[2,3-d]pyrimidines as anticancer agents, and will help scientists to design new selective, effective and safe anticancer agents. � 2023 The Royal Society of Chemistry.
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    MEK inhibitors in cancer treatment: structural insights, regulation, recent advances and future perspectives
    (Royal Society of Chemistry, 2023-08-10T00:00:00) Ram, Teja; Singh, Ankit Kumar; Kumar, Adarsh; Singh, Harshwardhan; Pathak, Prateek; Grishina, Maria; Khalilullah, Habibullah; Jaremko, Mariusz; Emwas, Abdul-Hamid; Verma, Amita; Kumar, Pradeep
    MEK1/2 are critical components of the RAS-RAF-MEK-ERK or MAPK signalling pathway that regulates a variety of cellular functions including proliferation, survival, and differentiation. In 1997, a lung cancer cell line was first found to have a MEK mutation (encoding MEK2P298L). MEK is involved in various human cancers such as non-small cell lung cancer (NSCLC), spurious melanoma, and pancreatic, colorectal, basal, breast, and liver cancer. To date, 4 MEK inhibitors i.e., trametinib, cobimetinib, selumetinib, and binimetinib have been approved by the FDA and several are under clinical trials. In this review, we have highlighted structural insights into the MEK1/2 proteins, such as the ?C-helix, catalytic loop, P-loop, F-helix, hydrophobic pocket, and DFG motif. We have also discussed current issues with all FDA-approved MEK inhibitors or drugs under clinical trials and combination therapies to improve the efficacy of clinical drugs. Finally, this study addressed recent developments on synthetic MEK inhibitors (from their discovery in 1997 to 2022), their unique properties, and their relevance to MEK mutant inhibition. � The Royal Society of Chemistry 2023.
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    Metal Complexes in Cancer Treatment: Journey So Far
    (John Wiley and Sons Inc, 2023-02-24T00:00:00) Kumar Singh, Ankit; Kumar, Adarsh; Singh, Harshwardhan; Sonawane, Pankaj; Pathak, Prateek; Grishina, Maria; Pal Yadav, Jagat; Verma, Amita; Kumar, Pradeep
    Metal complexes in cancer therapy have attracted much interest mainly because metals exhibit unique characteristics, such as redox activity, metal-ligand interaction, structure and bonding, Lewis acid properties etc. In 1965, Barnett Rosenberg serendipitously discovered the metal-based compound cisplatin, an outstanding breakthrough in the history of metal-based anticancer complexes and led to a new area of anticancer drug discovery. Many metal-based compounds have been studied for their potential anticancer properties. Some of these compounds have FDA approval for clinical use, while others are now undergoing clinical trials for cancer therapy and detection. In the present study, we have highlighted the primary mode of action of metallic complexes and all FDA-approved/under clinical trial drugs with reference to cancer treatment. This review also focuses on recent progress on metal-based complexes such as platinum, ruthenium, iron, etc. with potential anticancer activities. � 2023 Wiley-VHCA AG, Zurich, Switzerland.