Synthesis, spectroscopic analysis, and computational-based investigations on ‘azo-coumarin-Co(II)-galangin’ hybrids exhibit multipotential activities

Abstract

The present study synthesized a series of cobalt (II) metal ion frame hybrid candidates (6a–6f) bearing phyto-flavonol galangin with substituted aryl diazenyl coumarins, and further structural confirmation was validated by various spectral techniques, including NMR, ATR-FTIR, UV-vis, HPLC, XRD, etc. Therapeutic potency was investigated via PASS (prediction of activity spectra for substances), molecular docking, molecular dynamics simulation, prediction of toxicity, pharmacokinetics, and drug-likeness scores, along with the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), with their energy gaps (ΔE_H–L) to locate the most potential therapeutic candidates. The PASS prediction (Pa > Pi score) showed that proposed metal complexes have kinase inhibitors, antioxidative, and antischistosomal activities with potential molecular docking scores (> −7 kcal/mol) against selected targeted enzymes. Further, the MD-simulation (RMSD, RMSF, Rg, and H-bonds) of the most potential docking complex, ‘HER2-6d’, showed a minimum deviation similar to the standard drug (lapatinib) at 100 ns, indicating that 6d could be a potential noncovalent anticancer inhibitor. In addition, metal complexes possess a non-toxic and ideal drug-ability profiles, and positive electron space in an excited state increases the binding affinity towards target enzymes. Among all six ligands, 6c and 6d were the two most multipotent therapeutic agents from the above analyses. In summary, this could be a feasible approach towards the utilization of phytochemicals in mainstream therapeutic applications, where bioinformatics tools help to select a lead drug candidate at an early stage and guide for higher experimental success by proceeding with potential candidates.

Communicated by Ramaswamy H. Sarma

Keywords:

• Aryl-azo synthesis
• galangin
• coumarin derivatives
• cobalt(II) metal complex
• molecular docking-simulation
• toxicity and drug-likeness prediction

Acknowledgments

The authors are grateful to the higher authority of the Department of Health Research and the Indian Council of Medical Research, Govt. of India, New Delhi, for providing Dr. Shasank S. Swain with the DHR-Young Scientist and the ICMR-Post Doctoral Research Fund. We also want to thank the honourable director of ICMR-RMRC, the dean of the School of Pharmaceutical Sciences, and other associate research personnel for their support for this research work. We are also grateful to Salixiras Research Pvt. Ltd., Bhubaneswar, for providing high-end computational platforms for analysis and support.

Data availability statement

Data supporting the findings of this study are within this manuscript or available from the corresponding authors upon reasonable request.

Disclosure statement

The authors declare that they do not have any conflict of interest.

Additional information

Funding

This work was supported by the ICMR-Postdoctoral Fund (No. 3/1/3/PDF(21)/HRD-2019-2) from the Indian Council of Medical Research, Government of India, New Delhi.