Department Of Pharmaceutical Sciences and Natural Products

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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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    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.