Browsing by Author "Mohd Kamil Hussain"

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Design and Synthesis of Bioinspired Benzocoumarin-Chalcones Chimeras as Potential Anti-Breast Cancer Agents
(John Wiley and Sons Inc, 2021) Mohammad Saquib; Mohammad Hassan Baig; Mohammad Faheem Khan; Sarfuddin Azmi; Shahnaaz Khatoon; Arun Kumar Rawat; Jae June Dong; Mohammad Asad; Md. Arshad; Mohd Kamil Hussain
The design and synthesis of a library of natural product inspired benzocoumarin-chalcones chimeras, as potent and selective, novel, anti-breast cancer scaffold, is reported herein. Twenty-one new chimeric molecules, 25–45, were synthesized through an efficient protocol involving the Horner-Wadsworth-Emmons-olefination of β-aryl-β-ketophosphonates with 4-formyl-2H-benzo[h]chromen-2-ones as the key step, and evaluated for anti-proliferative activity against a panel of four breast cancer and related cell lines viz. MDA-MB-231 (ER-ve), MCF-7 (ER+ve), Ishikawa (endometrial cancer) and Hela (cervical cancer). The synthesized molecules showed in vitro anti-proliferative activity in a range of 7.42 to 74.68 μM (IC50). Compounds 33 and 34 showed very good activity, with 34 exhibiting better activity than the standard drugs, tamoxifen and raloxifene. Interestingly, none of the compounds showed cytotoxity against the normal human cell line. To identify the possible targets of the active compounds, molecular docking analysis was conducted to correlate their interaction with the ERα and ERβ receptors. From among the active compounds the docked conformations of 34, at the ERα and ERβ active sites, showed that it fits most favorably in the ligand binding space and shows hydrophobic interactions with the salient residues. Based on the above findings, 34 was identified as a lead molecule for development of more potent anti-breast cancer agents. © 2021 Wiley-VCH GmbH
Monoterpene Indole Alkaloids from Anthocephalus cadamba Fruits Exhibiting Anticancer Activity in Human Lung Cancer Cell Line H1299
(Wiley-Blackwell, 2018) Devendra Pratap Mishra; Mohsin Ali Khan; Dinesh Kumar Yadav; Arun Kumar Rawat; Rakesh Kumar Singh; Tanveer Ahamad; Mohd Kamil Hussain; Mohammad Saquib; Mohammad Faheem Khan
Two new monoterpene indole alkaloids, Vincosamide-N-oxide (1) and isodihydroamino cadambine (2) along with seven known alkaloids and triterpenoids vincosamide (3), vallesiachotamine (4), iso-vallesiachotamine (5), dihydrocadambine (6), cadambine (7), ursolic acid (8) and oleanolic acid (9) were isolated from the fruits of Anthocephalus cadamba (Roxb) Miq. (Family: Rubiaceae). The chemical structures of the isolated molecules were determined using a combination of InfraRed (IR) and one dimensional (1D) and two dimensional (2D) Nuclear Magnetic Resonance (NMR) spectroscopy and High Resolution-Electronspray Ionisation Mass Spectrometry (HR-ESIMS). The molecules were evaluated for their in-vitro antiproliferative activity against human lung cancer cell line H1299. Cytotoxic profile was studied in mouse macrophage RAW 264.7 cell line and induction of apoptosis in MCF-7 cells. Compounds 4 and 5 were found to exhibit potent anticancer activity with IC50 values of 4.24 and 3.79 μM respectively. Both compounds demonstrated significant fragmentation in the chromatin within the nucleus cells as a result of apoptosis. In addition none of the purified compounds showed any toxic effect on normal cells. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim