Phytocompounds are a well-established source of drug discovery due to their unique chemical and functional diversities. In the area of cancer therapeutics, several phytocompounds have been used till date to design and develop new drugs. One of the desired interests of pharmaceutical companies and researchers globally is that new anti-cancer leads are discovered, for which phytocompounds can be considered a valuable source. Simultaneously, in recent years, the growth of computational approaches like virtual screening (VS), molecular dynamics (MD), pharmacophore modelling, Quantitative structure–activity relationship (QSAR), Absorption Distribution Metabolism Excretion and Toxicity (ADMET), network biology, and machine learning (ML) has gained importance due to their efficiency, reduced time-consuming nature, and cost-effectiveness. Therefore, the present review amalgamates the information on plant-based molecules identified for cancer lead discovery from in silico approaches. The mandate of this review is to discuss studies published in the last 5–6 years that aim to identify the phytomolecules as leads against cancer with the help of traditional computational approaches as well as newer techniques like network pharmacology and ML. This review also lists the databases and webservers available in the public domain for phytocompounds related information that can be harnessed for drug discovery. It is expected that the present review would be useful to pharmacologists, medicinal chemists, molecular biologists, and other researchers involved in the development of natural products (NPs) into clinically effective lead molecules.
Graphical abstract
Reviewed the niche area of phytomolecule-based anti-cancer drug discovery with respect to current trends including machine learning.
Endometrial cancer (EC) is among the most common gynecological disorders globally. As single nucleotide polymorphisms (SNPs) play an important role in the causation of EC, therefore, a comprehensive meta-analysis of 49 SNPs covering 25,446 cases and 41,106 controls was performed to identify SNPs significantly associated with increased EC risk. PubMed was searched to identify case control studies and meta-analysis was performed to compute the pooled odds ratio (OR) at 95% confidence interval (CI). Cochran’s Q-test and I2 were used to study heterogeneity, based on which either a random or a fixed effect model was implemented. The meta-analysis identified 11 SNPs (from 10 genes) to be significantly associated with increased EC risk. Among these, seven SNPs were significant in at least three of the five genetic models, as well as three of the polymorphisms (rs1801320, rs11224561, and rs2279744) corresponding to RAD51, PGR, and MDM2 genes, which contained more than 1000 EC cases each and exhibited increased risk. The current meta-analysis indicates that polymorphisms associated with various hormone related genes—SULT1A1 (rs1042028), PGR (rs11224561), and CYP19A1 (rs10046 and rs4775936); DNA repair genes—ERCC2 (rs1799793), OGG1 (rs1052133), MLH1 (rs1800734), and RAD51 (rs1801320) as well as genes like MDM2 (rs2279744), CCND1 (rs9344), and SERPINE1 (rs1799889), are significantly associated with increased EC risk.
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