Antitubercular and antioxidant activities of hydroxy and chloro substituted chalcone analogues: Synthesis, biological and computational studies

Abstract

A series of chalcone analogues (1–15) were synthesized by Claisen-Schmidt condensation in good yields (70–95%) and characterized by FT-IR, 1H NMR and mass spectral methods. Additionally, compounds 3 and 7 were characterized by 13C NMR. Antitubercular and antioxidant activities of the chalcones were evaluated by MABA and DPPH free radical assays. In MABA assay analogues 3 (MIC = 14 ± 0.11 µM) and 11 (MIC = 14 ± 0.17 µM) bearing fluorine and methoxy groups at para and meta positions were 1.8-times more active than the standard pyrazinamide (MIC = 25.34 ± 0.22 µM). The chalcone analogues such as compound 7 (IC50 = 4 ± 1 µg/mL) containing electron releasing groups such as OH at ortho position had slightly more antioxidant activity than Gallic acid (IC50 = 5 ± 1 µg/mL). The potential compounds 3, 7, 9 and 11 were less selective and toxic against human live cell lines-LO2. Further, molecular docking results of chalcones against anti-tubercular drug target isocitrate lyase (PDB ID: 1F8M) revealed that compound 3 and 11 shown least binding energies as −7.6, and −7.5 kcal/mol are in line with in vitro MABA assay, suggesting that these compounds 3 and 11 are strong inhibitor of isocitrate lyase. SwissADME programme estimated the drug likeliness properties of compounds 3, 7, 9 and 11. The lead molecules arisen through this study helps to develop new antitubercular and antioxidant agents.

Keywords

• Hydroxy chalcones
• Chlorinated chalcones
• Antitubercular activity
• Antioxidant activity
• Autodock
• SwissADME