Pharmaceutical Sciences and Natural Products - Research Publications

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    Medicinal chemistry aspects and synthetic strategies of coumarin as aromatase inhibitors: an overview
    (Springer, 2022-12-05T00:00:00) Ratre, Pooja; Kulkarni, Swanand; Das, Sweety; Liang, Chengyuan; Mishra, Pradyumna Kumar; Thareja, Suresh
    Coumarin is a bicyclic oxygen bearing heterocyclic scaffold formed by fusion of benzene with the pyrone ring. Because of its unique physicochemical characteristics and the ease with which it may be transformed into a wide range of functionalized coumarins during�synthesis, coumarin provides a privileged scaffold for medicinal chemists. As a result, many coumarin derivatives have been developed, synthesized, and evaluated to target a variety of therapeutic domains, thereby making it an attractive template for designing novel anti-breast cancer compounds. The main culprit in estrogen overproduction in the estrogen-dependent breast cancer (EDBC), is the enzyme aromatase (AR), and it is thought to be a significant target for the effective treatment of EDBC. Considering coumarins versatility, this review presents a detailed overview of diverse study of aromatase as a target for coumarins. An overview of structure�activity relationship analysis of coumarin core is also included so as to summarize the desired pharmacophoric features essential for design and development of aromatase inhibitors (AIs) using coumarin core. Identification of key synthesis techniques that could aid researchers in designing and developing novel analogues with significant anti-breast cancer properties along with their mechanism of action have also been covered in the current review. Graphical Abstract: [Figure not available: see fulltext.] � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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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.
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    Coumarin Derivatives as Anticancer Agents for Lung Cancer Therapy: A Review.
    (Bentham Science, 2018) Kumar, Manvendra; Singla, Ramit; Jandriyal, Jyoti; Jaitak, Vikas
    Background: The prevalence of lung cancer is 14% among the newly diagnosed cancer cases worldwide. Currently, the number of drugs that are in clinical practice is having a high prevalence of side effect and multidrug resistance. Researchers have made an attempt to expand a suitable anticancer drug that has no MDR and side effect. Objective: Extensive exploration of Coumarin derivatives as a potent inhibitor of variety of proteins including EGFR, tyrosine kinase, ERK1/2, PI3K, HSP 90, Bax, STAT proteins, NF-κB and telomerase which have been associated with lung cancer. Method: The recent literature was surveyed utilizing the online resources and databases including scifinder, pubchem, EMBL, scopus and google scholar. Results: Upon analyzing the structure-activity relationship, it was found that N-aryl carboxamide, phenyl substitution at the C-3 position and 1,2,3- triazolyl, trihydroxystilbene, amino substitution at the C-4 position of the coumarin nucleus were the most effective in targeting lung cancer. Conclusion: This review is a collaborative and extensive compilation of synthetic strategies, mechanism of action, and the structure-activity relationship thereof for the management of lung carcinoma.