Browsing by Author "Singla R."

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Coumarin Derivatives as Anticancer Agents for Lung Cancer Therapy: A Review
(NLM (Medline), 2018) Kumar M.; Singla R.; Dandriyal J.; Jaitak V.
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-?B 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Design, synthesis and biological evaluation of novel indole-benzimidazole hybrids targeting estrogen receptor alpha (ER-?)
(Elsevier Masson SAS, 2018) Singla R.; Gupta K.B.; Upadhyay S.; Dhiman, Monisha; Jaitak V.
In the course of efforts to develop novel selective estrogen receptor modulators (SERMs), indole-benzimidazole hybrids were designed and synthesised by fusing the indole nucleus with benzimidazole. All the compounds were first inspected for anti-proliferative activity using ER-? responsive T47D breast cancer cell lines and ER-? binding assay. From this study, two representative bromo substituted compounds 5f and 8f were found to be most active and thus were escalated for gene expression studies for targeting ER-?. Cell imaging experiment clearly suggest that compounds were able to cross cell membrane and accumulate thus causing cytotoxicity. RT-PCR and Western blotting experiments further supported that both compounds altered the expression of mRNA and receptor protein of ER-?, thereby preventing the further transactivation and signalling pathway in T47D cells lines. Structural investigation from induced fit simulation study suggest that compound 5f and 8f bind in antagonistic conformation similar to bazedoxifene by extensive hydrogen bonding and Van der Waals forces. All these results strongly indicate that compound 5f and 8f represents a novel potent ER-? antagonist properties and will proved promising in the discovery of SERM for the management of breast cancer.
Stevia rebaudiana targeting ?-amylase: An in-vitro and in-silico mechanistic study
(Taylor and Francis Ltd., 2019) Singla R.; Singla N.; Jaitak V.
Diabetes mellitus (DM) is the fastest growing metabolic disorder in the world. Recently, more attention is paid to the study of natural products due to side effects of synthetic drugs. Stevia rebaudiana (Bertoni) is considered an encouraging starting point for the antidiabetic lead development. In the present study, the in vitro ?-amylase inhibitory activity of the extracts of S. rebaudiana is investigated. In order to understand the molecular mechanism and future pharmacophore development, in silico study of secondary metabolites isolated from S. rebaudiana was carried out. Results indicated that water extract shows highest ?-amylase inhibitory activity as compared to other extracts. Moreover, compound 20 (rebaudioside A) which has been previously reported and isolated from water extract showed the impressive binding profile with ?-amylase. Therefore, our study suggests that S. rebaudiana could be used in the development of therapeutic drugs for the treatment of diabetes.