Identification of potential inhibitors of thymidylate synthase (TS) (PDB ID: 6QXH) and nuclear factor kappa-B (NF–κB) (PDB ID: 1A3Q) from Capsicum annuum (bell pepper) towards the development of new therapeutic drugs against colorectal cancer (CRC)
Author:
Olajide Monsurat123, Abdul-Hammed Misbaudeen12ORCID, Bello Isah Adewale1, Adedotun Ibrahim Olaide2, Afolabi Tolulope Irapada2
Affiliation:
1. Department of Pure and Applied Chemistry , Ladoke Akintola University of Technology, Faculty of Pure and Applied Science , Along Ogbomoso Ilorin Expressway, Ladoke Akintola University Of Technology , Ogbomoso , Oyo , 210214 , Nigeria 2. Computational Biophysical Chemistry Laboratory, Department of Pure and Applied Chemistry , Ladoke Akintola University of Technology, Faculty of Pure and Applied Science , Ogbomoso , Oyo State , Nigeria 3. Department of Chemical Sciences , Crescent University Abeokuta , Abeokuta , Ogun State , Nigeria
Abstract
Abstract
Colorectal cancer is the third most deadly cancer globally. Drug resistance and attendant side effects make the available standard anti-colorectal cancer drugs against target receptors inefficient. Phytochemicals from medicinal plants are safer, cheaper, effective, and heal diseases from the cellular level. This study is aimed at identifying potential inhibitors of thymidylate synthase (TS) and nuclear factor kappa-B (NF–κB) target receptors from Capsicum annuum towards the development of new therapeutic drugs against colorectal cancer via in silico approach. One hundred and fifty (150) ligands previously reported from Capsicum annuum were downloaded from the PubChem database and were subjected to chemo-informatics analyses such as ADMET, drug-likeness, oral bioavailability, bioactivity, and PASS prediction to ascertain their therapeutic and safety profile before docking. The ligands that passed the analyses were docked against TS and NF–κB in duplicate using a creditable docking tool (PyRx). Raltitrexed and emetine were used as the standard drug inhibitors for TS and NF–κB, respectively. The results obtained from this study showed that feruloyl-beta-D-glucose (8.45 kcal/mol), 5-O-caffeoylquinic acid (−8.40 kcal/mol), 5-O-caffeoylquinic acid methyl ester (−7.89 kcal/mol), feruloyl hexoside (−7.40 kcal/mol), O-glucopyranoside (−7.55 kcal/mol), and quercetin (−7.00 kcal/mol) shared the same binding pocket with TS while feruloyl-beta-D-glucose (−7.00 kcal/mol), chlorogenic acid (−6.90 kcal/mol), 5-O-caffeoylquinic acid (−6.90 kcal/mol) and feruloyl hexoside (−6.50 kcal/mol) shared the same pocket with NF–κB. These compounds were selected as best hits due to their excellent inhibitory efficiency and chemoinformatic profiles. Thus, the compounds may function as prospective lead compounds for developing a new anti-colorectal cancer drug.
Publisher
Walter de Gruyter GmbH
Subject
General Physics and Astronomy,General Materials Science,General Chemistry
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