Dataset Information

In Silico Identification of 1-DTP Inhibitors of Corynebacterium diphtheriae Using Phytochemicals from Andrographis paniculata.

ABSTRACT: A number of phytochemicals have been identified as promising drug molecules against a variety of diseases using an in-silico approach. The current research uses this approach to identify the phyto-derived drugs from Andrographis paniculata (Burm. f.) Wall. ex Nees (AP) for the treatment of diphtheria. In the present study, 18 bioactive molecules from Andrographis paniculata (obtained from the PubChem database) were docked against the diphtheria toxin using the AutoDock vina tool. Visualization of the top four molecules with the best dockscore, namely bisandrographolide (-10.4), andrographiside (-9.5), isoandrographolide (-9.4), and neoandrographolide (-9.1), helps gain a better understanding of the molecular interactions. Further screening using molecular dynamics simulation studies led to the identification of bisandrographolide and andrographiside as hit compounds. Investigation of pharmacokinetic properties, mainly ADMET, along with Lipinski's rule and binding affinity considerations, narrowed down the search for a potent drug to bisandrographolide, which was the only molecule to be negative for AMES toxicity. Thus, further modification of this compound followed by in vitro and in vivo studies can be used to examine itseffectiveness against diphtheria.

SUBMITTER: Al-Khayri JM

PROVIDER: S-EPMC9862189 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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In Silico Identification of 1-DTP Inhibitors of Corynebacterium diphtheriae Using Phytochemicals from Andrographis paniculata.

Al-Khayri Jameel M JM Dubey Sakshi S Thirumoorthy Gopishankar G Nagella Praveen P Rezk Adel Abdel-Sabour AA Shehata Wael Fathi WF

Molecules (Basel, Switzerland) 20230116 2

A number of phytochemicals have been identified as promising drug molecules against a variety of diseases using an in-silico approach. The current research uses this approach to identify the phyto-derived drugs from Andrographis paniculata (Burm. f.) Wall. ex Nees (AP) for the treatment of diphtheria. In the present study, 18 bioactive molecules from Andrographis paniculata (obtained from the PubChem database) were docked against the diphtheria toxin using the AutoDock vina tool. V ...[more]

PMID: 36677967

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Project description:Natural products derived from plants play a vital role in the discovery of new drug candidates, and these are used for novel therapeutic drug development. Andrographis paniculata and Spilanthes paniculata are used extensively as medicinal herbs for the treatment of various ailments, and are reported to have neuroprotective properties. β-amyloid is a microscopic brain protein whose significant aggregation is detected in mild cognitive impairment and Alzheimer's disease (AD) brains. The accumulation of β-amyloid disrupts cell communication and triggers inflammation by activating immune cells, leading to neuronal cell death and cognitive disabilities. The proteases acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta secretase-1 (BACE-1) have been reported to be correlated with the synthesis and growth of β-amyloid plaques in the brains of AD patients. In the present study, the phenolic compounds from A. paniculata and S. paniculata that have been reported in the literature were selected for the current investigation. Furthermore, we employed molecular docking and molecular dynamics studies of the phenolic compounds with the proteins AChE, BChE, and BACE-1 in order to evaluate the binding characteristics and identify potent anti-amyloid agents against the neurodegenerative diseases such as AD. In this investigation, we predicted three compounds from A. paniculata with maximum binding affinities with cholinesterases and BACE-1. The computational investigations predicted that these compounds follow the rule of five. We further evaluated these molecules for in vitro inhibition activity against all the enzymes. In the in vitro investigations, 3,4-di-o-caffeoylquinic acid (5281780), apigenin (5280443), and 7-o-methylwogonin (188316) were found to be strong inhibitors of AChE, BChE, and BACE-1. These findings suggest that these compounds can be potent multi-target inhibitors of the proteases that might cumulatively work and inhibit the initiation and formation of β-amyloid plaques, which is a prime cause of neurotoxicity and dementia. According to our knowledge, these findings are the first report on natural compounds isolated from A. paniculata as multi-target potent inhibitors and anti-amyloid agents.

Dataset Information

In Silico Identification of 1-DTP Inhibitors of Corynebacterium diphtheriae Using Phytochemicals from Andrographis paniculata.

Publications

In Silico Identification of 1-DTP Inhibitors of <i>Corynebacterium diphtheriae</i> Using Phytochemicals from <i>Andrographis paniculata</i>.

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