IDENTIFYING TUBULIN AS A NEW TARGET OF A DIHYDROPYRIDINE DERIVATIVE, AMLODIPINE BESYLATE

The quest for new antimitotic drugs is an ongoing process where microtubules act as an attractive target for anti-cancer drugs. In this work, we report on the anti-cancer activity of Amlodipine besylate (AB), a salt derivative of the dihydropyridine groupdrug Amlodipine, a long-acting third-generation calcium channel blocker. Cytotoxicity assay revealed that AB demonstrated cytotoxic effects against cancer cells with greater specificity against cervical cancer cells (IC₅₀ 10 μM) whereas the non-cancerous NKE cells remained unaffected at this dose. AB inhibited HeLa cell migration as observed via scratch assay. Docking studies indicated that AB has the highest binding affinity for vinca site compared to Tubulin’s taxol, colchicine, and laulilamide binding domains. AB similarly interacted with tubulin to vinca and established two hydrophobic interactions with VAL³⁵³, PRO³²⁵; hydrogen bonds with ASN³²⁹, VAL¹⁷⁵ and THR²¹⁸ at the binding pocket. The stability of the Tubulin-AB complex was analyzed by molecular simulation studies. Further AB treated cells revealed altered microtubule architecture and drug-induced microtubule depolymerization in HeLa cells. More detailed study might unravel additional binding attributes of AB related to its antimitotic potential imparting valuable addition to the repurposing of existing medicines.