<b>Binding properties between curcumin and malarial tubulin: molecular-docking and </b><i><b>ab initio</b></i><b> fragment molecular orbital calculations</b>

Abstract

Curcumin can bind to tubulin and inhibit the formation of tubulin polymer, which contributes to the formation of microtubule. Binding sites of curcumin on the α-and β-tubulin heterodimer were predicted by a molecular docking study to ascertain probable causes for the observed anti-microtubule effects of curcumin. However, the specific interactions between curcumin and the tubulins have yet to be elucidated at an electronic level. We here investigated the binding properties between curcumin and α-or β-tubulin of Plasmodium falciparum, using ab initio fragment molecular orbital (FMO) calculations, in order to reveal the preferable binding sites of curcumin on these tubulins. The results were compared with those for some microtubule destabilizing drugs evaluated by the same method to confirm the efficiency of curcumin as an inhibitor to the tubulins. Our ab initio FMO calculations might provide useful information for proposing novel therapeutic agents with significant binding affinity to both the α-and β-tubulins.

Multiple Virtual Screening Strategies for the Discovery of Novel Compounds Active Against Dengue Virus: A Hit Identification Study

“…The solvated interaction energy (SIE) method is a fast calculation with moderate accuracy. Based on the divide and conquer algorithm [30], the fragment molecular orbital (FMO) method can provide the detailed interaction energies with high accuracy [31,32].…”

Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods

“…The mechanism for the antitumor activity of natural compound curcumin were related with multiple signaling pathways, such as the signal transducer, nuclear factor-κB, cyclooxygenase 2, mitogen-activated protein kinase, and activator of transcription 3, and TNF-α signaling pathways. Curcumin is a spectrum inhibitor that targets epidermal growth factor receptor ( Gopal, 2022 ), protein kinase C ( Hasmeda and Polya, 1996 ), tubulin ( Chakraborti et al, 2011 ; Ota et al, 2018 ), cyclin-dependent kinase 2 ( Sumirtanurdin et al, 2020 ), casein kinase 2 ( Cozza et al, 2020 ), adenosine monophosphate-activated protein kinases ( Soltani et al, 2019 ), and Abelson leukemia virus tyrosine kinase 1 ( Rodrigues et al, 2021 ). A previous study reported that curcumin exhibits antitumor activity in triple-negative breast cancer patient-derived xenograft tumor mice by inhibiting the expression of salt-inducible kinase 3 (SIK3) ( Cheng et al, 2021 ).…”

Conservation of dinitroani-line/phosphorothioamidate site of α-tubulin in Plasmodium species distributed in India

“…It is a fact that many of existing now malaria therapeutics are increasingly ineffective and it is an urgent need in development of principally new therapeutic strategies and agents. During last ten years there has been a new growth of interest in tubulin as an important antiprotozoan target [6,7] Several classes of microtubule (MT) inhibitors have demonstrate potent activity against malarial parasites in in vivo: vinblastine [8][9][10], dolastatin 10 [11], auristatins [12] and taxoids [13,14]. Most of these agents have been demonstrated to disrupt or stabilize normal microtubular structures.…”