Synthetic and Naturally Occurring Heterocyclic Anticancer Compounds with Multiple Biological Targets

Abstract

Cancer is a complex group of diseases initiated by abnormal cell division with the potential of spreading to other parts of the body. The advancement in the discoveries of omics and bio- and cheminformatics has led to the identification of drugs inhibiting putative targets including vascular endothelial growth factor (VEGF) family receptors, fibroblast growth factors (FGF), platelet derived growth factors (PDGF), epidermal growth factor (EGF), thymidine phosphorylase (TP), and neuropeptide Y4 (NY4), amongst others. Drug resistance, systemic toxicity, and drug ineffectiveness for various cancer chemo-treatments are widespread. Due to this, efficient therapeutic agents targeting two or more of the putative targets in different cancer cells are proposed as cutting edge treatments. Heterocyclic compounds, both synthetic and natural products, have, however, contributed immensely to chemotherapeutics for treatments of various diseases, but little is known about such compounds and their multimodal anticancer properties. A compendium of heterocyclic synthetic and natural product multitarget anticancer compounds, their IC50, and biological targets of inhibition are therefore presented in this review.

Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment

“…Te core structures found in the 86 scafolds included O, N, and S-heterocycles comprising indole, thiazole, isochromene, acridine-1,9-dione, imidazoline-2,4-dione, isoindoline-1,3dion, pyrazolo[4,3-c]pyridine, pyrido [4,3,b]indole, and 1,38triazaspiro [4,5]dione. Te medicinal properties of these heterocycles have been reported for the treatment of cancer, leishmaniasis, diabetes mellitus, and malaria [65][66][67]. Among the ten best scoring scafolds (Supplementary Table 1) to dutasteride, CHEMBL337492 and CHEMBL583325 (Supplementary Table 1) which are epimers of each other with a bis-(trifuoromethyl)benzene moiety were found to show a similarity score of 0.6055 and 0.56708, respectively.…”

Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line

“…It improves the solubility of the drug and its candidacy as a good drug molecule. Earlier, we reported the synthesis of various structural hybrids of oxadiazole-based acetamide [ 26 , 27 , 28 , 29 ], and it has been proven from the literature that heterocycle-based compounds possess good anti-cancer activity [ 30 ]. Thus, in an extension of our earlier research on heterocycles, –COOH group of 2-(4-isobutylphenyl)propanoic acid was cyclized into a 1,2,4-triazole ring 4.…”

Synthesis of novel pyrimido[4,5‐b]quinolines as potential anticancer agents and HER2 inhibitors

“…Heterocycle‐based compounds are privileged scaffolds in anticancer drug discovery as they can easily target various metabolic pathways and cellular process in cancer pathology (Amewu et al, 2021; Chaurasiya et al, 2023; Lang et al, 2020). One of the most advantageous heterocycles is pyrimido[4,5‐ b ]quinoline which has been investigated in the recent years as a pharmacophore with versatile pharmacological activities in addition to anticancer activity (Abbas et al, 2011; Alqasoumi et al, 2010; Eghtedari et al, 2022; Ghorab et al, 2009, 2012; El‐Gazzar et al, 2009; Panchabhai et al, 2021).…”