School Of Basic And Applied Sciences

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    Application of curcumin nanoformulations to target folic acid receptor in cancer: Recent trends and advances
    (Academic Press Inc., 2023-06-20T00:00:00) Hussain, Arif; Kumar, Ajay; Uttam, Vivek; Sharma, Uttam; Sak, Katrin; Saini, Reena V.; Saini, Adesh K.; Haque, Shafiul; Tuli, Hardeep Singh; Jain, Aklank; Sethi, Gautam
    Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy. � 2023 Elsevier Inc.
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    Evolving strategies and application of proteins and peptide therapeutics in cancer treatment
    (Elsevier Masson s.r.l., 2023-05-05T00:00:00) Mukherjee, Anirban Goutam; Wanjari, Uddesh Ramesh; Gopalakrishnan, Abilash Valsala; Bradu, Pragya; Biswas, Antara; Ganesan, Raja; Renu, Kaviyarasi; Dey, Abhijit; Vellingiri, Balachandar; El Allali, Achraf; Alsamman, Alsamman M.; Zayed, Hatem; George Priya Doss, C.
    Several proteins and peptides have therapeutic potential and can be used for cancer therapy. By binding to cell surface receptors and other indicators uniquely linked with or overexpressed on tumors compared to healthy tissue, protein biologics enhance the active targeting of cancer cells, as opposed to the passive targeting of cells by conventional small-molecule chemotherapeutics. This study focuses on peptide medications that exist to slow or stop tumor growth and the spread of cancer, demonstrating the therapeutic potential of peptides in cancer treatment. As an alternative to standard chemotherapy, peptides that selectively kill cancer cells while sparing healthy tissue are developing. A mountain of clinical evidence supports the efficacy of peptide-based cancer vaccines. Since a single treatment technique may not be sufficient to produce favourable results in the fight against cancer, combination therapy is emerging as an effective option to generate synergistic benefits. One example of this new area is the use of anticancer peptides in combination with nonpeptidic cytotoxic drugs or the combination of immunotherapy with conventional therapies like radiation and chemotherapy. This review focuses on the different natural and synthetic peptides obtained and researched. Discoveries, manufacture, and modifications of peptide drugs, as well as their contemporary applications, are summarized in this review. We also discuss the benefits and difficulties of potential advances in therapeutic peptides. � 2023
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    Boron in cancer therapeutics: An overview
    (Elsevier Inc., 2023-10-17T00:00:00) Kulkarni, Swanand; Bhandary, Dyuti; Singh, Yogesh; Monga, Vikramdeep; Thareja, Suresh
    Boron has become a crucial weapon in anticancer research due to its significant intervention in cell proliferation. Being an excellent bio-isosteric replacement of carbon, it has modulated the anticancer efficacy of various molecules in the development pipeline. It has elicited promising results through interactions with various therapeutic targets such as HIF-1?, steroid sulfatase, arginase, proteasome, etc. Since boron liberates alpha particles, it has a wide-scale application in Boron Neutron Capture therapy (BNCT), a radiotherapy that demonstrates selectivity towards cancer cells due to high boron uptake capacity. Significant advances in the medicinal chemistry of boronated compounds, such as boronated sugars, natural/unnatural amino acids, boronated DNA binders, etc., have been reported over the past few years as BNCT agents. In addition, boronated nanoparticles have assisted the field of bio-nano medicines by their usage in radiotherapy. This review exclusively focuses on the medicinal chemistry aspects, radiotherapeutic, and chemotherapeutic aspects of boron in cancer therapeutics. Emphasis is also given on the mechanism of action along with advantages over conventional therapies. � 2023 Elsevier Inc.
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    Developing our knowledge of the quinolone scaffold and its value to anticancer drug design
    (Taylor and Francis Ltd., 2023-08-18T00:00:00) Singh, Yogesh; Bhatia, Neha; Biharee, Avadh; Kulkarni, Swanand; Thareja, Suresh; Monga, Vikramdeep
    Introduction: The quinolone scaffold is a bicyclic benzene-pyridinic ring scaffold with nitrogen at the first position and a carbonyl group at the second or fourth position. It is endowed with a diverse spectrum of pharmacological activities, including antitumor activity, and has progressed into various development phases of clinical trials for their target-specific anticancer activity. Areas covered: The present review covers both classes of quinolones, i.e. quinolin-2(H)-one and quinolin-4(H)-one as anticancer agents, along with their possible mode of binding. Furthermore, their structure-activity relationships, molecular mechanisms, and pharmacokinetic properties are also covered to provide insight into their structural requirements for their rational design as anticancer agents. Expert opinion: Synthetic feasibility and ease of derivatization at multiple positions, has allowed medicinal chemists to explore quinolones and their chemical diversity to discover newer anticancer agents. The presence of both hydrogen bond donor (?NH) and acceptor (-C=O) functionality in the basic scaffold at two different positions, has broadened the research scope. In particular, substitution at the -NH functionality of the quinolone motif has provided ample space for suitable functionalization and appropriate substitution at the quinolone�s third, sixth, and seventh carbons, resulting in selective anticancer agents binding specifically with various drug targets. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
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    Synthesis, biological evaluation and in-silico ADME studies of novel series of thiazolidin-2,4-dione derivatives as antimicrobial, antioxidant and anticancer agents
    (BioMed Central Ltd, 2022-09-15T00:00:00) Kumar, Harsh; Kumar, Davinder; Kumar, Pradeep; Thareja, Suresh; Marwaha, Minakshi Gupta; Navik, Umashanker; Marwaha, Rakesh Kumar
    Background: A novel series of thiazolidine-2,4-dione molecules was derived and their chemical structures were established using physiochemical parameters and spectral techniques (1H-NMR, IR, MS etc.). The synthesized molecule were then evaluated for their antioxidant, anticancer and antimicrobial potential. Results and discussion: Serial tube dilution method was employed to evaluate the antimicrobial potential against selected fungal and bacterial strains by taking fluconazole and cefadroxil as reference antifungal and antibacterial drugs respectively. 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity was used to assess the antioxidant potential of the synthesized analogues. Further, the anticancer potential of the selected molecules was assessed against DU-145 cancer cell lines using MTT assay. The drug-likeness was also evaluated by studying in-silico ADME parameters of the synthesized analogues. Conclusion: In antioxidant evaluation studies, the analogue H5 with IC50 = 14.85�?g/mL was found to be the most active molecule. The antimicrobial evaluation outcomes suggested that the molecules H5, H13, H15 and H18 possessed moderate to promising activity against the selected species of microbial strains having MIC range 7.3��M to 26.3��M. The results of anticancer evaluation revealed that all the screened derivatives possess mild anticancer potential. The in-silico ADME studies revealed that all the compounds were found to be drug-like. � 2022, The Author(s).
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    Flavonoids as promising anticancer agents: an in silico investigation of ADMET, binding affinity by molecular docking and molecular dynamics simulations
    (Taylor and Francis Ltd., 2022-09-27T00:00:00) Biharee, Avadh; Yadav, Arpita; Jangid, Kailash; Singh, Yogesh; Kulkarni, Swanand; Sawant, Devesh M.; Kumar, Pradeep; Thareja, Suresh; Jain, Akhlesh Kumar
    Cancer is one of the most concerning diseases to humankind. Various treatment strategies are being employed for its treatment, out of which use of natural products is an essential one. Flavonoids have proven to be promising anticancer targets since decades. Also, tubulin is a significant biological target for the development of anticancer agents due to its crucial role in mitosis and abundance throughout the body. In the current study, in silico ADMET parameters of 104 flavonoids were examined, followed by molecular docking with the colchicine binding site of Tubulin protein (PDB; Id 4O2B). The best conformation from each flavonoid subcategory with the best docking score (MolDock score) was further subjected to 100 ns of molecular dynamics to investigate the protein-ligand complex�s stability. Different parameters such as RMSD, RMSF, rGy and SASA were calculated for the six flavonoids using molecular dynamic studies. The top most compound from all the six subcategories of flavonoids elicited best behavior in the colchicine binding site of Tubulin protein. This in silico study employing molecular docking and molecular dynamics simulation provides strong evidence for flavonoids to be excellent anti-tubulin agents for the treatment of cancer. Communicated by Ramaswamy H. Sarma. � 2022 Informa UK Limited, trading as Taylor & Francis Group.
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    Design, synthesis and evaluation of 4-phenyl-1,2,3-triazole substituted pyrimidine derivatives as antiproliferative and tubulin polymerization inhibitors
    (Elsevier B.V., 2022-06-26T00:00:00) Dwivedi, Ashish Ranjan; Kumar, Vijay; Yadav, Ravi Prakash; Kumar, Naveen; Jangid, Kailash; Anand, Piyush; Sharma, Deepak Kumar; Barnawal, Somesh; Kumar, Vinod
    Ligands binding to the colchicine domain of the tubulin protein act as tubulin polymerization inhibitors and arrest the cell cycle in G2/M phase. A series of 4-Phenyl-1,2,3-triazole substituted pyrimidine derivatives have been synthesized and evaluated for antiproliferative and antitubulin activities. In the series, AV-6 and AV-14 were found to be active against the three tested cancer cell lines wherein AV-6 displayed IC50 values of 1.2 �M, 5.5 �M, and 1.9 �M while AV-14 displayed IC50 values of 4.7 �M, 1.7 �M, and 1.4 �M against HCT-116, MCF-7 and HT-29 cell lines, respectively. These compounds were found to be non toxic to the normal cells (HEK-293). In the cell cycle analysis and JC-1 studies, these compounds induce mitocondria mediated apoptosis. In the tubulin polymerization inhibition studies, AV-6 displayed significant tubulin polymerization inhibition potential. In the molecular docking and simulation studies, these compounds fit well in the active site of colchicine. � 2022 Elsevier B.V.
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    Thiazole and Related Heterocyclic Systems as Anticancer Agents: A Review on Synthetic Strategies, Mechanisms of Action and SAR Studies
    (Bentham Science Publishers, 2022-03-21T00:00:00) Sahil; Kaur, Kamalpreet; Jaitak, Vikas
    Background: Cancer is the second leading cause of death worldwide. Many anticancer drugs are commercially available, but lack of selectivity, target specificity, cytotoxicity, and development of resistance lead to serious side effects. Several experiments have been going on to develop compounds with minor or no side effects. Objective: This review mainly emphasizes synthetic strategies, SAR studies, and mechanism of action if thiazole, benzothiazole, and imidazothiazole-containing compounds as anticancer agents. Methods: Recent literature related to thiazole and thiazole-related derivatives endowed with encouraging anticancer potential is reviewed. This review emphasizes contemporary strategies used for the synthesis of thiazole and related derivatives, mechanistic targets, and comprehensive structural activity relationship studies to provide perspective into the rational design of high-efficiency thiazole-based anticancer drug candidates. Results: Exhaustive literature survey indicated that thiazole derivatives are associated with properties of inducing apoptosis and disturbing tubulin assembly. Thiazoles are also associated with the inhibition of NFkB/mTOR/PI3K/AkT and regulation of estrogenmediated activity. Furthermore, thiazole derivatives have been found to modulate critical targets, such as topoisomerase and HDAC. Conclusion: Thiazole derivatives seem to be quite competent and act through various mechanisms. Some of the thiazole derivatives, such as compounds 29, 40, 62, and 74a with IC50 values of 0.05 ?M, 0.00042 ?M, 0.18 ?M, and 0.67 ?M, respectively, not only exhibit anticancer activity, but they also have lower toxicity and better absorption. Therefore, some other similar compounds could be investigated to aid in the development of anticancer pharmacophores. � 2022 Bentham Science Publishers.
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    Molecular Docking and In Vitro Anticancer Screening of Synthesized Arylthiazole linked 2H-indol-2-one Derivatives as VEGFR-2 Kinase Inhibitors
    (Bentham Science Publishers, 2021-11-18T00:00:00) Shalmali, Nishtha; Bawa, Sandhya; Ali, Md Rahmat; Kalra, Sourav; Kumar, Raj; Zeya, Bushra; Rizvi, Moshahid Alam; Partap, Sangh; Husain, Asif
    Background: Indoline-2,3-dione comprises a leading course group of heterocycles endowed with appealing biological actions, including anticancer activity. There are significant justifications for exploring the anticancer activity of Schiff base derivatives of isatin as a vast number of reports have documented remarkable antiproliferative action of isatin nucleus against various cancer cell lines. Aims and Objectives: A series of arylthiazole linked 2H-indol-2-one derivatives (5a-t) was designed and synthesized as potential VEGFR-2 kinase inhibitors keeping the essential pharmacophoric features of standard drugs, like sunitinib, sorafenib, nintedanib, etc. They were evaluated for their in vitro anticancer activity. The aim of this study was to investigate and assess the anticancer potential of isatin-containing compounds along with their kinase inhibition activity. Methods: The title compounds were synthesized by reacting substituted isatins with para-substituted arylthiazoles using appropriate reaction conditions. Selected synthesized derivatives went under preliminary screening against a panel of 60 cancer cell lines at NCI, the USA, for single-dose and five dose assays. Molecular docking was performed to explore the binding and interactions with the active sites of the VEGFR-2 receptor (PDB Id: 3VHE). Derivatives 5a, 5b, 5c, 5d, 5g, 5h, and 5m were assessed for in vitro inhibition potency against Human VEGFR-2 using ELISA (En-zyme-Linked Immunosorbent Assay) kit. All the target compounds were determined against human colon cancer cell line SW480 (colorectal adenocarcinoma cells). Cellular apoptosis/necrosis was determined by flow cytometry using annexin V-FITC. DNA content of the cells was analyzed by flow cytometry and the cycle distribution was quantified. Results: Compounds 5a and 5g exhibited noteworthy inhibition during a five-dose assay against a panel of 60 cell lines with MID GI50 values of 1.69 and 1.54 �M, respectively. Also, both the lead compounds 5a and 5g demonstrated promising VEGFR-2 inhibitory activity with IC50 values of 5.43�0.95 and 9.63�1.32 �M, respectively. The aforesaid potent compounds were found effective against SW480 (colorectal adenocarcinoma cells) with IC50 values of 31.44 �M and 106.91 �M, respectively. Compound 5a was found to arrest the cell cycle at the G2/M phase, increasing apoptotic cell death. The docking study also supported VEGFR-2 inhibitory activity as both compounds 5a and 5g displayed promising binding and interactions with the active sites of VEGFR-2 receptor (PDB: 3VHE) with docking scores-9.355 and-7.758, respectively. All the compounds obeyed Lipinski�s rule of five. Conclusion: Indoline-2,3-dione and thiazole have huge potential to be considered a steer combination approach for developing promising kinase inhibitors as cancer therapeutics. � 2022.
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    Design, synthesis and anticancer activity of 2-arylimidazo[1,2-a]pyridinyl-3-amines
    (Academic Press Inc., 2021-11-01T00:00:00) Yadav, Umesh Prasad; Ansari, Arshad J.; Arora, Sahil; Joshi, Gaurav; Singh, Tashvinder; Kaur, Harsimrat; Dogra, Nilambra; Kumar, Raj; Kumar, Santosh; Sawant, Devesh M.; Singh, Sandeep
    A series of imido-heterocycle compounds were designed, synthesized, characterized, and evaluated for the anticancer potential using breast (MCF-7 and MDA-MB-231), pancreatic (PANC-1), and colon (HCT-116 and HT-29) cancer cell lines and normal cells, while normal cells showed no toxicity. Among the screened compounds, 4h exhibited the best anticancer potential with IC50 values ranging from 1 to 5.5 ?M. Compound 4h caused G2/M phase arrest and apoptosis in all the cell lines except MDA-MB-231 mammosphere formation was inhibited. In-vitro enzyme assay showed selective topoisomerase II? inhibition by compound 4h, leading to DNA damage as observed by fluorescent staining. Cell signalling studies showed decreased expression of cell cycle promoting related proteins while apoptotic proteins were upregulated. Interestingly MDA-MB-231 cells showed only cytostatic effects upon treatment with compound 4h due to defective p53 status. Toxicity study using overexpression of dominant-negative mutant p53 in MCF-7 cells (which have wild type functional p53) showed that anticancer potential of compound 4h is positively correlated with p53 expression. � 2021 Elsevier Inc.