Microwave Assisted Synthesis and Antimicrobial Activities of Carboxylpyrazoline Derivatives: Molecular Docking and DFT Influence in Bioisosteric Replacement

Chalcone is a naturally derived compound which has well-known for its antimicrobial potency. Different factors reduced the efficiency of drug derivatives effective drugs always remain in demand. In this present work, bioisosteric replacement of carboxyl group is described in 1a–h, 2a–h, 3a–h and 4a–h) via microwave-assisted synthesis with excellent yields (46.76–94.59%). The antimicrobial evaluation against S. aureus depicted excellent inhibition of 1b, 1h and 3a–h with higher inhibition zones (11–18 mm) compared to that of ampicillin (11 mm). The structure-activity relationship was supported by molecular docking studies of 1b and 3h on S. aureus 4-pql protein with the binding affinity of −6.7 and −7.8 kcal/mol respectively. The DFT studies depicted the energy gap (ΔE) values 4.12 eV and 4.48 eV for compounds 1b and 3h, respectively. The presence of electron-withdrawing group (EWG) of fluorine substituent on the pyrazoline network has increased the antimicrobial activity as compared to chalcone derivatives. This study is profitable to medicinal industries in designing new drugs that benefit mankind. (Figure presented.).