Biological evaluation of 2-pyrazolinyl-1-carbothioamide derivatives against HCT116 human colorectal cancer cell lines and elucidation on QSAR and molecular binding modes. Issue 20 (15th October 2017)

• Record Type: Journal Article
• Authors: Kim, Beom Soo; Shin, Soon Young; Ahn, Seunghyun; Koh, Dongsoo; Lee, Young Han; Lim, Yoongho
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 20(2017)
• Page Start: 5423
• Page End: 5432
• Publication Date: 2017-10-15
• Subjects: 2-Pyrazolinyl-1-carbothioamide -- Colorectal cancer -- Clonogenicity -- In silico docking -- Abl kinase; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.07.062
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: In the search of compounds exhibiting anticancer activity, 37 derivatives of 2-pyrazolinyl-1-carbothioamide were designed and synthesized. Clonogenic cell survival assays were adapted to measure the cytotoxicities of the synthetic derivatives against HCT116 human colon cancer cell lines. Half-maximal cell growth inhibitory concentrations (GI50 ) ranged from 0.49 to 41.22 µM. The compound with the lowest GI50 value, 3-(2-hydroxy-4, 5-dimethoxyphenyl)-5-(naphthalen-1-yl)- N -(3, 4, 5-trimethoxyphenyl)-pyrazolinyl-1-carbothioamide, was subjected to further biological studies, including cell viability and apoptosis assays to examine levels of annexin-V in the outer plasma membrane layer and poly ADP-ribose polymerase cleavage. Additionally, in vitro kinase assays were performed, and Abelson murine leukemia viral oncogene homolog 1 (Abl 1) tyrosine kinase demonstrated good inhibitory activity. The binding mode between the compound of interest and Abl 1 was elucidated using in silico docking. The pharmacophores derived for 2-pyrazolinyl-1-carbothioamides based on their quantitative structure–activity relationships will help us design novel chemotherapeutic agents.