In-silico investigation of curcumin drug-likeness, gene-targets and prognostic relevance of the targets in panels of human cancer cohorts

David B Oshevire David B Oshevire,Opeyemi N Hassan Opeyemi N Hassan,Bashir Lawal Bashir Lawal,Jonathan Ibrahim Jonathan Ibrahim,Peter I Ugwunnaji Peter I Ugwunnaji,Eustace B Berinyu Eustace B Berinyu,Abdulfatai Ismail Abdulfatai Ismail,Hassana H Badeggi Hassana H Badeggi,Aishatu Mustapha Aishatu Mustapha,Blessing U Alozieuwa Blessing U Alozieuwa

doi:10.30574/gscbps.2021.14.1.0002

Abstract

Despite advancements in diagnostic and standard treatment modalities, cancer survival rate remains disappointing globally. It has however, been recognized that exploring the therapeutic properties of secondary metabolite from natural products may alleviate the problems of drug resistance and toxicity that besiege the conventional therapies, and hence improve the overall prognosis of cancer patient. To this end curcumin, a polyphenolic natural compound has been widely studied for it anticancer activities in in vitro and in vivo models. Computational technology has significantly improved the success rate of drug discovery and development, hence, it has become a widely explore tool in drug candidate identification. In this study we used computational approached to identify 12 genes that are potential druggable candidate for curcumin. The genes identified were found to be enriched in cancer and drug resistance associated signaling pathways. Interestingly, the top 3 identified genes; Microtubule-associated protein tau (MAPT), Toll-like receptor 9 (TLR9) and Tyrosyl-DNA phosphodiesterase 1 (TDP1) were observed to be over expressed in multiple cancer cohorts and were associated with poor prognoses of the patients. Curcumin has good physicochemical, bioavailability and ADMET properties. Importantly, it met the Lipinski's Rule of 5 for drug likeness and thus worthy of further in vitro and in vivo confirmation studies.

Highlights

Despite advancements in diagnostic and standard treatment modalities, cancer remain second leading cause of death worldwide [1]
It is on this note that we conducted medicinal chemistry, pharmacokinetic (ADMET) studies and “drug-likeness” using Lipinski's rule of five on curcumin (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl) hepta-1,6-diene-3,5-dione) (Figure 1A) to determine their activity within the human body
Our findings revealed that curcumin has acceptable physicochemical and bioavailability properties (Figure 1C and Table 1)

Summary

Introduction

Despite advancements in diagnostic and standard treatment modalities, cancer remain second leading cause of death worldwide [1]. Natural products are diverse in terms of structure and biological activities [5,6,7,8] and offer superior therapeutic options and safety than the conventional and synthetic compounds used in high throughput screening processes in drug discovery and development pipelines [9]. Computational technology has significantly minimized the experimental drug trials and improve the success rate of drug discovery and development, it has become a widely explore tool in drug candidate identification [21]. To this end, we conducted an in silico drug likeness and target predictions studies on curcumin with a view of unraveling the potential targets that could be implicated in it diverse anti-cancer activities

Material and methods

Results and discussion

Curcumin target are enriched in cancer associated signaling pathways

Conclusion