In silico design of a new Podophyllotoxin derivative with potent anti-tubulin activity

Abstract

Nowadays, there is an increasing focus on cancer as a major cause of death. Therefore, comprehending the chemical reactivity, geometric and electronic structures of inhibitors can aid in the development of better quality and more efficient drugs. In this study, we propose a hybrid compound of Podophyllotoxin (PPT) and vitamin C (VC) as an anti-cancer agent. The PPT and its derivatives are well-known for their anti-tubulin properties. The geometry optimisation and calculation of global chemical reactivity indices (µ = −3.836 eV, η = 2.402 eV, S = 0.416 eV, and ω = 3.061 eV) were performed using the M06/6-311++G (d, p) level of theory. The global reactivity descriptors predict that the PPT-VC compound has more nucleophilic properties compared to Etoposide and Teniposide compounds. Furthermore, the PPT-VC compound exhibits a lower HOMOPPT-VC–LUMOSWCNT gap and a higher adsorption energy (−37.4 kJ mol−1) in the encapsulation process than other derivatives into SWCNT, providing additional evidence of its nucleophilic nature as an effective anti-tubulin agent. Therefore, the PPT-VC@SWCNT compound can be considered a reliable drug delivery system (DDS). Molecular docking analysis reveals that the best cavity of tubulin has an interaction energy of −102.1 kJ mol−1, involving both bonding and non-bonding interactions.