An investigative study of antitumor properties of a novel thiazolo[4,5-d]pyrimidine small molecule revealing superior antitumor activity with CDK1 selectivity and potent pro-apoptotic properties
Mohamed, Sameh H; Elgiushy, Hossam R; Hammad, Sherif F; Abou-Taleb, Nageh A; A M Abouzid, Khaled; Abouzid, Khaled; Hassan, Zeinab; Ali Taha, Heba;
Abstract
New thiazolo[4,5-d]pyrimidine analogues were synthesized and biologically assessed in-vitro for their antineoplastic activity. The growth inhibitory effects of these compounds were assessed through the National Cancer Institute-United States of America (NCI-USA) anticancer screening program. Compound5(7-Chloro-3-(2,4-dimethoxyphenyl)-5-methylthiazolo[4,5-d]pyrimidine-2(3H)-thione) was found to have a potent and broad-spectrum cytotoxic action against NCI panel with GI50 (50% growth inhibition concentration) mean graph midpoint (MG-MID) = 2.88 µM. MTT assay was used to determine IC50 values of the most potent agent against HCT-116 colorectal carcinoma and WI-38 human lung fibroblast cell lines; 5.33 µM ± 0.69 and 21.69 µM ± 1.04, respectively. Flow cytometric analysis revealed that compound5triggered apoptosis and G2/M cell cycle arrest. The ability of compound5to inhibit CDK1 (Cyclin-Dependent Kinase 1)/Cyclin B complex was evaluated, and its IC50 value was 97 nM ± 2.33. Moreover, according to the gene expression analysis, compound5up-regulated p53, BAX, cytochrome c, caspases-3,-8 and-9 besides down-regulated Bcl-2. In conclusion, compound5exerted a potent pro-apoptotic activity through the activation of the intrinsic apoptotic pathway and arrested the cell cycle at the G2/M phase.
Other data
Title | An investigative study of antitumor properties of a novel thiazolo[4,5-d]pyrimidine small molecule revealing superior antitumor activity with CDK1 selectivity and potent pro-apoptotic properties | Authors | Mohamed, Sameh H; Elgiushy, Hossam R; Hammad, Sherif F; Abou-Taleb, Nageh A; A M Abouzid, Khaled; Abouzid, Khaled ; Hassan, Zeinab; Ali Taha, Heba | Keywords | Apoptosis; Cell cycle arrest;Anticancer activity;Thiazolo[4,5-d]pyrimidine | Issue Date | 1-Sep-2020 | Publisher | PERGAMON-ELSEVIER SCIENCE LTD | Journal | Bioorganic & medicinal chemistry | Volume | 28 | Issue | 17 | ISSN | 0968-0896 | DOI | 10.1016/j.bmc.2020.115633 | PubMed ID | 32773088 | Scopus ID | 2-s2.0-85087883266 | Web of science ID | WOS:000557982900008 |
Recommend this item
Similar Items from Core Recommender Database
Items in Ain Shams Scholar are protected by copyright, with all rights reserved, unless otherwise indicated.