化学
李宾斯基五定律
立体化学
磺酰罗丹明B细胞培养试剂染料
蒂奥-
异丙基
细胞毒性
嘧啶
细胞培养
组合化学
药理学
生物化学
体外
有机化学
生物信息学
医学
生物
遗传学
基因
作者
Khursheed Ahmad Sheikh,Darakhshan Parveen,Mohammad Mumtaz Alam,Faizul Azam,Mohammad Ahmed Khan,Mymoona Akhter,Sharba Tasneem,. Meenu,Suhel Parvez,Khalid Imtiyaz,Abbas Rizvi,Mohammad Shaquiquzzaman
标识
DOI:10.1016/j.bioorg.2024.107336
摘要
In this series we report the structure-based design, synthesis and anticancer activity evaluation of a series of eighteen cyclopropylamine containing cyanopyrimidine derivatives. The computational predictions of ADMET properties revealed appropriate aqueous solubility, high GI absorption, no BBB permeability, no Lipinski rule violations, medium total clearance and no mutagenic, tumorigenic, irritant and reproductive toxic risks for most of the compounds. Compounds VIIb, VIIi and VIIm emerged as the most potent anticancer agents among all compounds evaluated against 60 cancer cell lines through the one-dose (10 µM) sulforhodamine B assay. Further, the multiple dose cell viability studies against cancer cell lines MOLT-4, A549 and HCT-116 revealed results consistent with the one-dose assay, besides sparing normal cell line HEK-293. The three potent compounds also displayed potent LSD1 inhibitory activity with IC50 values of 2.25, 1.80 and 6.08 µM. The n-propyl-thio/isopropyl-thio group bonded to the pyrimidine ring and unsubstituted/ electron donating group (at the para- position) attached to the phenyl ring resulted in enhanced anticancer activity. However, against leukemia cancer, the electron donating isopropyl group remarkably enhanced anti-cancer activity. Our findings provide important leads, which merit further optimization to result in better cancer therapeutics.
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