In silico elucidation and network pharmacology analysis of phytochemicals from Elephantorrhiza elephantina and Pentanisia prunelloides for antitubercular activity

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-01-31 DOI:10.1016/j.genrep.2025.102155

Alaiha Zaheen , Pinki Francina Lefalo , Sanchaita Rajkhowa , Subrata Sinha

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Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health challenge, exacerbated by drug-resistant strains. Phytochemicals, bioactive compounds from plants, offer a promising avenue for new drug development due to their diverse biological activities. This study focuses on two traditional medicinal plants, Elephantorrhiza elephantina and Pentanisia prunelloides, to identify potential anti-tuberculosis compounds. The compounds were initially evaluated for drug-likeness, followed by ADMET (absorption, distribution, metabolism, excretion, and toxicity) screening. Five compounds meeting these criteria were selected for further analysis. The 3D structures of these compounds were analyzed using PharmMapper to identify potential protein targets, focusing on those relevant to Mycobacterium tuberculosis. Protein-protein interaction networks were analyzed using STRING and Cytoscape to identify key hub genes. Additionally, KEGG pathway analysis was conducted with KOBAS to elucidate the biological processes, molecular functions, and cellular components involved. Homology modeling was performed using ITASSER to predict the 3D structure of target proteins. Finally, molecular docking studies were carried out to evaluate the binding interactions between the selected compounds and the MurF protein of Mycobacterium tuberculosis, followed by molecular dynamics simulations to assess the stability and conformational changes of the resulting protein-ligand complex over time. Among the compounds, arabinose (CID439195) demonstrated the strongest binding affinity to MurF, suggesting its potential as an anti-TB agent. These findings suggest that Elephantorrhiza elephantina and Pentanisia prunelloides hold significant potential for the development of new anti-tuberculosis therapies. This study underscores the importance of integrating computational approaches in drug discovery and highlights the promising role of phytochemicals in addressing global health challenges such as tuberculosis.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.