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

A series of chalcone analogues (1-15) were synthesized by Claisen-Schmidt condensation in good yields (70-95%) and characterized by FT-IR, H-1 NMR and mass spectral methods. Additionally, compounds 3 and 7 were characterized by C-13 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 mu M) and 11 (MIC = 14 +/- 0.17 mu M) 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 mu M). The chalcone analogues such as compound 7 (IC50 = 4 +/- 1 mu g/mL) containing electron releasing groups such as -OH at ortho position had slightly more antioxidant activity than Gallic acid (IC50 = 5 +/- 1 mu g/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. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.