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

Abstract

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.

Synthesis and Pharmacological Activities of Chalcone and Its Derivatives Bearing N-Heterocyclic Scaffolds: A Review

“…This suggests that the degree of electronegativity played a key role in modulating the physicochemical properties of the derivative (Figure 3). 17 Thus, the current Review presents the various synthetic protocols used to prepare chalcones incorporated with Nheterocyclic moieties and their wide spectrum of biological activities.…”

“…On top of this, many researchers are exhaustively devoted to synthesizing a chalcone derivative incorporating a heterocyclic scaffold. Chalcones incorporating heterocyclic scaffolds have been reported with various biological and pharmacological activities, such as antioxidant activity, 12 antibacterial activity, 12 antifungal activity, 13 antileishmanial activity, 14 anti-inflamatory activity, 15 anticancer activity, 16 antitubercular activity, 17 antiproliferative agents, 17 antimalarial activity, 18 antiplatelet activity, 19 carbonic anhydrase inhibitors, 20 an inhibitor of microsomalenzyme glutathione-S-transferases, 21 and CYP1 enzyme inhibitors. 22 Chalcones with an N-heterocyclic moiety such as pyrrole, imidazole, thiazole, pyrazole, oxazole, isooxazole, pyridine, pyrazoline, indole, benzothiazole, benzimidazole, and quinoline scaffolds play a significant role in the area of medicine.…”

Antitubercular activity assessment of fluorinated chalcones, 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studies

“…A blue color in the well was interpreted as no bacterial growth, and pink color was scored as growth. The MIC was defined as lowest drug concentration which prevented the color change from blue to pink [ 50 , 51 ]. Additionally, cLogP of all the target compounds has been calculated using SwissADME software.…”

Chalcone: A Promising Bioactive Scaffold in Medicinal Chemistry

“…The results indicated that structures ( 57 ) and scaffolds enhance the activity [ 96 ]. Thiazole-based chalcones ( 58 ) showed more promising activity than the standard drug pyrazinamide, with MIC values of 2.43 µM [ 104 ].…”