Conjugation of Curcumin and Metformin for Improved Pharmacological Profile in Cancer Therapy: An In Silico Approach

Abstract

Curcumin has been shown to possess high cytotoxicity towards various cell lines. But its low aqueous solubility and bioavailability limit its use as an effective cytotoxic agent. It has been reported that metformin selectively kills cancer stem cells and blocks tumor growth. Preclinical studies show the effectiveness of both curcumin and metformin in breast cancer. Conjugation of metformin and curcumin may result in synergistic cancer therapy by improving the aqueous solubility of curcumin and hence its bioavailability. In the present study, curcumin-metformin conjugate and the free drugs curcumin and metformin were subjected to docking analysis against the breast cancer targets such as epidermal growth factor receptor, kinesin spindle protein, cyclin-dependent kinase, human placental aromatase, and human estrogen receptor. Docking studies were performed using Autodock Vina. The results signify that curcumin-metformin conjugate showed higher binding energy ranging between -7.4 to -9.7 Kcal/mol than curcumin and metformin. The stability of the conjugate-receptor complex and interactions between them was further evaluated by molecular dynamics simulation. The results showed that the conjugate can interact effectively with human placental aromatase and can be considered for further studies.