ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Unveiling the molecular interplay between a novel chromene derivative and DNA: a multifaceted investigation

Dipak Kumar Sahoo, Nilima Priyadarsini Mishra, Shamasoddin Shekh, and Emmanuel E. Etim

Woxsen University, Hyderabad, India

E-mail: dipak.sahoo@woxsen.edu.in

Received: 27 May 2024  Accepted: 8 August 2024

Abstract:

This study comprehensively investigates the interactions between a new chromene derivative, 8-methoxy-3-nitro-2-(4-methoxyphenyl)-2H-chromene (MMNC), and DNA using a combination of experimental and computational techniques. MTT assays demonstrated MMNC’s potent anticancer activity against various cell lines, with lower IC50 values than the clinically used drug 5-fluorouracil. Spectroscopic techniques including circular dichroism, dynamic light scattering, UV–visible absorption, and fluorescence quenching experiments revealed that MMNC interacts with DNA at its minor groove without significantly altering its overall structure. The binding constant (Ka) was determined to be 3.09 × 10³ M⁻¹, indicating moderate groove binding. Molecular docking simulations supported the experimental findings, showing MMNC favorably binds to the DNA minor groove with a docking score of − 2.5 kcal/mol and binding free energy of − 26 kcal/mol. DFT studies provided insights into MMNC's electronic properties, with a HOMO–LUMO energy gap of 3.14 eV suggesting good reactivity. ADME/Tox analysis confirmed MMNC's drug-like properties, with no violations of Lipinski's rule of five or Jorgensen's rule of three. The comprehensive results demonstrate MMNC's promising potential as an anticancer agent and provide a foundation for rational design of improved chromene-based drugs.

Graphical abstract

Keywords: Drug discovery; The half-maximal inhibitory concentration (IC50); Molecular docking simulation; Density functional theory; Anticancer activity; ADME/Tox analysis

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-024-03654-5

Chemical Papers 78 (14) 8045–8057 (2024)