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

Abstract

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 K_b 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 K_b 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

Keywords:

• DNA binding
• protein binding
• molecular docking
• cytotoxicity assay
• ADME study

Acknowledgements

The authors are thankful to the Head, Department of Chemistry, Sardar Patel University, for providing necessary research facilities; Department of Science and Technology-Promotion of University Research and Scientific Excellence (DST-PURSE) for LC-MS analysis; Center of Advanced Study (CAS)-Phase-II and University Grants Commission-Center with Potential for Excellence in Particular Area (UGC-CPEPA) program for providing instrumental and chemicals facilities. Furthermore, we are very thankful to Ganpat University for the plagiarism check using the TURNITIN software.

Disclosure statement

No potential conflict of interest was reported by the authors.