Molecular dynamics simulation, synthesis and topoisomerase inhibitory actions of vanillin derivatives: a systematic computational structural integument

• Published in: Journal of biomolecular structure & dynamics Vol. 40; no. 22; pp. 11653 - 11663
• Main Authors: Sahoo, Chita Ranjan, Paidesetty, Sudhir Kumar, Sarathbabu, Subbarayan, Dehury, Budheswar, Senthil Kumar, Nachimuthu, Padhy, Rabindra Nath
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2022
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Benzaldehydes - pharmacology; breast cancer; Breast Neoplasms; caspase; Cell Proliferation; Female; Humans; molecular docking; Molecular Docking Simulation; molecular dynamics; Molecular Dynamics Simulation; Molecular Structure; Structure-Activity Relationship; sulfanilamide; synthesis; Vanillin; synthesis; molecular docking; breast cancer; Vanillin; molecular dynamics; sulfanilamide; caspase
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2021.1961867

A series of 4-hydroxy-3-methoxy benzaldehyde (vanillin) derivatives (3a-3r) was designed for the principle of Schiff base condensation with several individual sulfanilamide analogues. The inhibitory potencies of the designed compounds were evaluated through molecular docking simulation studies against the targets, breast cancer-topo isomerase-IIα and estrogen receptor-α; and the top scoring poses with higher binding energy were selected to assess the mode of binding and stability of each complex through molecular dynamics simulations. Compounds that remained stable in the active sites of the both target receptors through a number of strong H-bonds and hydrophobic contacts were selected. Based on the computational results, these selected compounds, 3b, 3e and 3f were synthesized and were followed up for structural elucidation attempts, by FT/ATR, 1 H NMR and 13 C NMR. From the experimental in vitro studies on 3b, 3e and 3f, the following remarkable activities against breast cancer cell line were done; IC 50 values of 3b, 3e and 3f were noted, 6.7, 4.3 and 11 ng/mL, respectively. These newly synthesized compounds may be used as novel inhibitors of nuclear receptors with potential therapeutic applications in control of cancer. Communicated by Ramaswamy H. Sarma