Pharmaceutical Sciences and Natural Products - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/56

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    Synthesis and in-silico Studies of 4-phenyl Thiazol-2-amine Derivatives as Putative Anti-breast Cancer Agents
    (Bentham Science Publishers, 2023-03-22T00:00:00) Lavanya, Kanamarlapudi Joshna; Kaur, Kamalpreet; Jaitak, Vikas
    Background: Breast cancer (BC) is the second-leading cause of cancer-related fatalities in women after lung cancer worldwide. The development of BC is significantly influenced by estrogen receptors (ERs). The problem with current cancer treatments is selectivity, target specificity, cytotoxicity, and developing resistance. Thiazole scaffolds are gaining popularity in drug discovery due to their broad range of biological activity. It has the extraordinary capacity to control a variety of cellular pathways, and its potential for selective anticancer activity can be explored. Objective: Synthesis and in-silico studies of 4-Phenyl thiazol-2-amine derivatives as anti-breast cancer agents and molecular docking was used to assess the compounds� capacity to bind ER-? protein target. Methods: In this study, 4-Phenylthiazol-2-amine derivatives (3a-j) have been synthesized, and using Schrodinger software, molecular docking and ADME studies of the compounds were conducted. Results: Most of the synthesized compounds have shown dock scores ranging from-6.658 to 8.911 kcal/mol, which is better than the standard drug tamoxifen (-6.821 kcal/mol). According to molecular docking, all compounds fit in the protein�s active site and have the same hydrophobic pocket as the standard drug tamoxifen. Further, all of the compounds� ADME properties are below acceptable limits. Conclusion: Compound 3e showed the best docking score of-8.911. All compounds� ADME properties are within acceptable limits, and their p/o coefficients fall within a range, suggesting they will all have sufficient absorption at the site of action. These compounds can be evaluated invitro and in-vivo in the future. � 2024 Bentham Science Publishers.
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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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    Synthesis, in vitro, and docking analysis of c-3 substituted coumarin analogues as anticancer agents
    (Bentham Science Publishers, 2020-01-28T00:00:00) Thakur, Anuradha; Kaur, Kamalpreet; Sharma, Praveen; Singla, Ramit; Singh, Sandeep; Jaitak, Vikas
    Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin cancer. Estrogen receptors (ERs) play an important role in the progression of BC. Current anticancer agents have several drawbacks such as serious side effects and the emergence of resistance to chemotherapeutic drugs. As coumarins possess minimum side effects along with multidrug reversal activity, it has a tremendous ability to regulate a diverse range of cellular pathways that can be explored for selective anticancer activity. Objectives: Synthesis and evaluation of new coumarin analogues for anti-proliferative activity on human breast cancer cell line MCF-7 along with exploration of binding interaction of the compounds for ER-? target protein by molecular docking. Methods: In this study, the anti-proliferative activity of C-3 substituted coumarins analogues (1-17) has been evaluated against estrogen receptor-positive MCF-7 breast cancer cell lines. Molecular interactions and ADME study of the compounds were analyzed by using Schrodinger software. Results: Among the synthesized analogues, 12 and 13 show good antiproliferative activity with IC50 values 1 and 1.3 ?M, respectively. Molecular docking suggests a remarkable binding pose of all the seventeen compounds. Compounds 12 and 13 were found to exhibit a docking score of -4.10 kcal/mol and -4.38 kcal/mol, respectively. Conclusion: Compounds 12 and 13 showed the highest activity followed by 1 and 5. ADME properties of all compounds were in the acceptable range. The active compounds can be taken for lead optimization and mechanistic interventions for their in vivo study in the future. � 2021 Bentham Science Publishers.
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    Synthesis and In Silico Studies of C-4 Substituted Coumarin Analogues as Anticancer Agents
    (Bentham Science Publishers, 2020-06-29T00:00:00) Dandriyal, Jyoti; Kaur, Kamalpreet; Jaitak, Vikas
    Background: Coumarin is a fused ring system and possesses the enormous capability of targeting various receptors participating in the cancer pathway. Coumarin and its derivatives were found to exhibit very rare toxicity and other side effects. It has been found its immense anticancer potential depends on the nature of the group present and its pattern of substitution on the basic nu-cleus. Objectives: Synthesis of C-4 substituted coumarin derivatives and to study their molecular interactions with ER? for the anticancer activity for Breast Cancer. Methods: C-4 substituted coumarins analogues (1-10) have been synthesized using conventional heating and microwave irradiation. Using Schrodinger software, molecular modeling studies were carried out and ADME properties of the compounds were predicted. Results: All the synthesized compounds have shown better G-Score (-6.87 to-8.43 kcal/mol) as compared to the standard drug tamoxifen (-5.28kcal/mol) and auraptene (-3.89kcal/mol). Molecular docking suggests that all compounds fit in the active site of protein as they have the same hydro-phobic pocket as standard drug tamoxifen, and have an acceptable range of ADME properties. Conclusion: Microwave-assisted synthesis showed better results as compared to conventional heat-ing. In silico studies revealed that all the compounds befit in the active site of the protein. ADME properties showed that all compounds are in allowable limits for human oral absorption. In the fu-ture, there is a possibility of in vitro and in vivo studies of the synthesized compounds. � 2021 Bentham Science Publishers.