4-Bromo-1,8-Naphthalimide derivatives as Antifungal Agents: Synthesis, Characterization, DNA Binding, Molecular docking, Antioxidant and ADMET studies

Abstract

A series of heterocyclic derivatives (2a-2n) was synthesized and characterized by melting point, FT-IR ¹H, ¹³C NMR, UV-visible spectroscopy and mass spectrometry. In vitro antifungal activity of the heterocyclic derivatives (2a-2n) was evaluated against the fungal strains: C. albicans, C. glabrata and C. tropicalis. The results revealed that heterocyclic analog 2a exhibits significant activity against all three strains with MIC value of 200 μg/mL, 2b exhibits antifungal activity against C. albicans with MIC value of 400 μg/mL and C. glabrata and C. tropicalis with MIC value of 500 μg/mL. Analog 2m also shows antifungal activity against C. albicans with MIC values of 200 μg/mL and C. glabrata and C. tropicalis with a MIC value 250 μg/mL as compared to the standard drug fluconazole. The binding interaction study of promising heterocyclic derivatives 2a, 2b, and 2m with CT-DNA was carried out by using UV-visible, fluorescence, cyclic voltammetry, circular dichroism, and viscosity measurements. The molecular docking study of the heterocyclic derivatives (2a–2n) was done with PDB ID: 1BNA. The pharmacokinetics properties of the heterocyclic derivatives (2a–2n) showed good oral bioavailability. Antioxidant potential of heterocyclic derivatives (2a–2n) was further approximated through DPPH and H₂O₂ free radical and showed that all the derivatives exhibited remarkable antioxidant activity.

Keywords:

• Heterocyclic derivatives
• antifungal activity
• CT-DNA binding
• molecular docking
• antioxidant properties

Acknowledgments

The authors are thankful to Prof. Nahid Nishat, Head of the Department of Chemistry for providing the necessary facilities. Prof. S. Ikram, Dr. Rahisuddin, and Prof. Saber M. Abd-Allah also acknowledge to Indo-Egypt Joint Project, DST, New Delhi for financial assistance (F. No. DST/INT/Egypt/P-05/2019). Nouman also thanks to the CSIR, New Delhi, India for Senior Research Fellowship (09/466(0229)/2019)-EMR-I.

Disclosure statement

No potential conflict of interest was reported by the author(s).