Synthetic approach toward spiro quinoxaline-β-lactam based heterocyclic compounds: Spectral characterization, SAR, pharmacokinetic and biomolecular interaction studies.

Series of spiro quinoxaline-β-lactam based heterocyclic compounds (QL 1 - QL 21) were synthesized and characterized by spectroscopic techniques like 1H-NMR, LC-MS, FT-IR spectroscopy and elemental analysis. The binding mode and binding strength between compounds and calf thymus-DNA were estimated by UV-visible spectroscopy, viscosity measurement and molecular docking studies. The compounds bind with the DNA through partial intercalation mode. In the absorption titration experiment, the Kb values for all the synthesized compounds were found in the range of 0.24-0.64 × 105 M-1. The protein binding studies of all the synthesized compounds were evaluated by absorption titration experiment, and the Kb value for all the compounds was obtained in the range of 0.030-1.571 × 104 M-1. The compounds were screened against two Gram (+ve) and three Gram (-ve) bacteria for antimicrobial activity. The MIC values for all the synthesized compounds were found in 95-255 µM. The LC50 values (cytotoxicity) of the synthesized compounds (QL 1-QL 21) were found in the range of 4.00-12.89 µg/mL. The ADME study was carried out using the online platform SwissADME and admetSAR to evaluate the pharmacokinetic profile of all the synthesized compounds. All the compounds were screened for anticancer activity against the human osteosarcoma (MG-63) cell line. The result shows that all the compounds exhibit effective anticancer activity.Communicated by Ramaswamy H. Sarma.