ABSTRACT
O. gratissimum is one of the most common medicinal plants in every community in Nigeria. This plant has been presumed to be useful in the management of diseases including breast cancer, which is one the commonest cancers affecting women globally. Hence, this study aimed to computationally investigate the phytochemicals present in O. gratissimum by elucidate their binding dynamics against five selected molecular targets of breast cancer and predict their pharmacokinetics properties. Molecular docking, MMGBSA calculation and ADMET prediction were used. The results showed that isovitexin has the highest binding affinity of -9.11 kcal/mol and -9.80 kcal/mol for Human Epidermal Growth Factor Receptor 2 (HER2) and Epidermal Growth Factor Receptor (EGFR) respectively. Rosmarinic acid has the highest binding affinity of -12.15 kcal/mol for Phosphatidylinositol 3-kinase (PI3K), Nepetoidin A has the highest binding affinity of -9.14 kcal/mol for oestrogen receptor (ER), and Vitexin has the highest binding affinity of -12.90 kcal/mol for Progesterone receptor (PR). MMGBSA provided total binding energy that confirmed the stability of the complexes under physiological conditions. The ADMET profiles showed that O. gratissimum top phytochemicals identified would be safe for oral administration with no hepatoxicity. Overall, this study identified isovitexin, vitexin, rosmarinic acid, nepetoidin A and luteolin among others, as compounds that exhibit strong anti-cancer properties against breast cancer cells.
ABSTRACT
BACKGROUND: Asthma is a chronic and complex pulmonary condition that affects the airways. A total of 250,000 asthma-related deaths are recorded annually and several proteins including chymase, spleen tyrosine kinase, and prostaglandin D2 receptor have been implicated in the pathophysiology of asthma. Different anti-inflammatory drugs have been developed for the treatment of asthma, particularly corticosteroids, but the associated adverse reactions cannot be overlooked. It is therefore of interest to identify and develop small molecule inhibitors of the integral proteins associated with asthma that have very little or no side effects. Herein, a molecular modeling approach was employed to screen the bioactive compounds in Chromolaena odorata and identify compounds with high binding affinity to the protein targets. RESULTS: Five compounds were identified after rigorous and precise molecular screening namely (-)-epicatechin, chlorogenic acid, ombuine, quercetagetin, and quercetin 3-O-rutinoside. These compounds generally showed impressive binding to all the targets understudy. However, chlorogenic acid, quercetagetin, and quercetin 3-O-rutinoside showed better prospects in terms of triple-action inhibition. Further pulmonary and oral pharmacokinetics showed positive results for all the reported compounds. The generated pharmacophore model showed hydrogen bond donor, hydrogen bond acceptor, and aromatic rings as basic structural features required for triple action inhibition. CONCLUSION: These findings suggest that these compounds could be explored as triple-action inhibitors of the protein targets. They are, therefore, recommended for further analysis.
ABSTRACT
Background: The search for ideal drugs with absolute antiviral activity against SARS-CoV-2 is still in place, and attention has been recently drawn to natural products. Several molecular targets have been identified as points of therapeutic intervention. The targets used in this study include SARS-CoV-2 helicase, spike protein, RNA-dependent RNA polymerase, main protease, and human ACE-2. An integrative computer-aided approach, which includes molecular docking, pharmacophore modeling, and pharmacokinetic profiling, was employed to identify anthocyanins with robust multiple antiviral activities against these SARS-CoV-2 targets. Result: Four anthocyanins (Delphinidin 3-O-glucosyl-glucoside, Cyanidin 3-O-glucosyl-rutinoside, Cyanidin 3-(p-coumaroyl)-diglucoside-5-glucoside), and Nasunin) with robust multiple inhibitory interactions were identified from a library of 118 anthocyanins using computer-aided techniques. These compounds exhibited very good binding affinity to the protein targets and moderate pharmacokinetic profiles. However, Cyanidin 3-O-glucosyl-rutinoside is reported to be the most suitable drug candidate with multiple antiviral effects against SARS-CoV-2 due to its good binding affinity to all five protein targets engaged in the study. Conclusions: The anthocyanins reported in this study exhibit robust binding affinities and strong inhibitory molecular interactions with the target proteins and could be well exploited as potential drug candidates with potent multiple antiviral effects against COVID-19.
