Thiazole–Chalcone Hybrids as Prospective Antitubercular and Antiproliferative Agents: Design, Synthesis, Biological, Molecular Docking Studies and In Silico ADME Evaluation

Molecules

Ravindra Nagasuri¹  AfzalB. Shaik²  RichieR. Bhandare³  Indrajeet Singhvi⁴  AshokBabu Kasetti⁵ 

[1] A.M. Reddy Memorial College of Pharmacy, Narasaraopeta, Andhra Pradesh 523316, India;Department of Pharmaceutical Chemistry, Vignan Pharmacy College, Vadlamudi, Guntur, Andhra Pradesh 522213, India;Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, Ajman University, Ajman P.O. Box 346, United Arab Emirates;Faculty of Pharmacy, Pacific Academy of Higher Education and Research University, Pacific University, Udaipur 313003, India;Research Scholar, Faculty of Pharmacy, Pacific Academy of Higher Education and Research University, Pacific University, Udaipur 313003, India;

关键词: thiazole;    chalcone;    antiproliferative activity;    antitubercular activity;    cytotoxic activity;    AutoDock;   

DOI  :  10.3390/molecules26102847

来源: DOAJ

【 摘 要 】

Compounds bearing thiazole and chalcone pharmacophores have been reported to possess excellent antitubercular and anticancer activities. In view of this, we designed, synthesized and characterized a novel series of thiazole–chalcone hybrids (1–20) and further evaluated them for antitubercular and antiproliferative activities by employing standard protocols. Among the twenty compounds, chalcones 12 and 7, containing 2,4-difluorophenyl and 2,4-dichlorophenyl groups, showed potential antitubercular activity higher than the standard pyrazinamide (MIC = 25.34 µM) with MICs of 2.43 and 4.41 µM, respectively. Chalcone 20 containing heteroaryl 2-thiazolyl moiety exhibited promising antiproliferative activity against the prostate cancer cell line (DU-145), higher than the standard methotrexate (IC₅₀ = 11 ± 1 µM) with an IC₅₀ value of 6.86 ± 1 µM. Furthermore, cytotoxicity studies of these compounds against normal human liver cell lines (L02) revealed that the target molecules were comparatively less selective against L02. Additional computational studies using AutoDock predicted the key binding interactions responsible for the activity and the SwissADME tool computed the in silico drug likeliness properties. The lead compounds generated through this study, create a way for the optimization and development of novel drugs against tuberculosis infections and prostate cancer.

【 授权许可】

Unknown