Discovery of a novel benzimidazole conjugated quinazolinone derivative as a promising SARS-CoV-2 3CL protease inhibitor.

Autor: Hue BTB; College of Natural Sciences, Can Tho University Can Tho 94000 Vietnam btbhue@ctu.edu.vn., Nguyet Huong Giang H; Department of Biological Science and Technology, National Yang Ming Chiao Tung University Hsinchu 30010 Taiwan tkwmll@nycu.edu.tw., Nguyen CQ; College of Natural Sciences, Can Tho University Can Tho 94000 Vietnam btbhue@ctu.edu.vn., Chou FP; Department of Biological Science and Technology, National Yang Ming Chiao Tung University Hsinchu 30010 Taiwan tkwmll@nycu.edu.tw.; Center for Emergent Functional Matter Science, National Yang Ming Chiao Tung University 1001 Ta-Hsueh Rd. Hsinchu 30010 Taiwan., La Duc Thanh D; College of Natural Sciences, Can Tho University Can Tho 94000 Vietnam btbhue@ctu.edu.vn.; Department of Material Science, National Yang Ming Chiao Tung University 1001 Ta-Hsueh Rd. Hsinchu 30010 Taiwan linhc@nycu.edu.tw., Tran Q; College of Natural Sciences, Can Tho University Can Tho 94000 Vietnam btbhue@ctu.edu.vn., Hieu VT; College of Natural Sciences, Can Tho University Can Tho 94000 Vietnam btbhue@ctu.edu.vn., Hoang Phuong Mai L; College of Natural Sciences, Can Tho University Can Tho 94000 Vietnam btbhue@ctu.edu.vn., Lin HC; Department of Material Science, National Yang Ming Chiao Tung University 1001 Ta-Hsueh Rd. Hsinchu 30010 Taiwan linhc@nycu.edu.tw.; Center for Emergent Functional Matter Science, National Yang Ming Chiao Tung University 1001 Ta-Hsueh Rd. Hsinchu 30010 Taiwan., Wu TK; Department of Biological Science and Technology, National Yang Ming Chiao Tung University Hsinchu 30010 Taiwan tkwmll@nycu.edu.tw.; Center for Emergent Functional Matter Science, National Yang Ming Chiao Tung University 1001 Ta-Hsueh Rd. Hsinchu 30010 Taiwan.
Jazyk: angličtina
Zdroj: RSC advances [RSC Adv] 2024 Oct 24; Vol. 14 (46), pp. 33820-33829. Date of Electronic Publication: 2024 Oct 24 (Print Publication: 2024).
DOI: 10.1039/d4ra03267e
Abstrakt: This report presents the design and synthesis of quinazolinone-based derivatives as promising SARS-CoV-2 3CL protease inhibitors. Two novel series, namely, febrifugine analogues 4a-i and quinazolinone conjugated benzimidazoles 9a-c, were successfully synthesized starting from isatoic anhydride. The synthesized quinazolinone derivatives were evaluated for their cytotoxicity against cancer cell lines and SARS-CoV-2 3CL inhibitory activity. The results showed that the synthesized compounds did not have significant toxicity for the non-cancer HEK293 cell line and MCF-7, MDA-MB-231, HEPG2 and HEPG2.2.15 cancer cell lines. Notably, compound 9b exhibited anti-3CL enzymatic activity in a dose-dependent manner, with the calculated IC 50 value of 10.73 ± 1.17 μM. Docking results highlighted the interaction between 9b and 3CL protease through hydrogen bonding with key amino acids, including His41, Met49, Cys145, Met165, Arg188, His164, and Glu166, at the active site of the protease. Pharmacokinetic studies and ADME analyses provide valuable insights into the potential of compound 9b as a drug candidate. These findings support the new scaffold as a candidate for 3CL pro inhibition and advanced anti-coronavirus drug research.
Competing Interests: There are no conflicts to declare.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
Externí odkaz: