Recent Developments in Oxazole Derivatives as Anticancer Agents: Review on Synthetic Strategies, Mechanism of Action and SAR Studies

Abstract

Background: Cancer is the world’s third deadliest disease. Despite the availability of numerous treatments, researchers are focusing on the development of new drugs lacking resistance and toxicity issues. Many newly synthesized drugs fail to reach clinical trials due to poor pharmacokinetic properties. Therefore, there is an imperative requisite to expand novel anticancer agents with in vivo efficacy. Objective: This review emphasizes synthetic methods, contemporary strategies used for the inclusion of oxazole moiety, mechanistic targets along with comprehensive structure-activity relationship studies to provide perspective into the rational design of highly efficient oxazole-based anticancer drugs. Methods: Literature related to oxazole derivatives engaged in cancer research is reviewed. This article gives a detailed account of synthetic strategies, targets of oxazole in cancer, including STAT3, Microtubules, G-quadruplex, DNA topoisomerases, DNA damage, Protein kinases, miscellaneous targets, in vitro studies, and some SAR studies. Results : Oxazole derivatives possess potent anticancer activity by inhibiting novel targets such as STAT3 and G-quadruplex. Oxazoles also inhibit tubulin protein to induce apoptosis in cancer cells. Some other targets such as DNA topoisomerase enzyme, protein kinases, and miscellaneous targets including Cdc25, mitochondrial enzymes, HDAC, LSD1, HPV E2 TAD, NQO1, Aromatase, BCl-6, Estrogen receptor, GRP-78, and Keap-Nrf2 pathway are inhibited by oxazole derivatives Many derivatives showed excellent potencies on various cancer cell lines with IC50 values in nanomolar concentrations. Conclusion: Oxazole is a five-membered heterocycle, with oxygen and nitrogen at 1 and 3 positions respectively. It is often combined with other pharmacophores in the expansion of novel anticancer drugs. In summary, oxazole is a promising entity to develop new anticancer drugs.

Photochemical three-component assembly of tri-substituted oxazoles through a carbenic phosphorus-nitrile hybrid ylide formation/trapping cascade

“…1A ). 2 Consequently, the development of efficient methods for preparing oxazole scaffolds has been a hot and challenging topic for organic synthetic chemists. 3 In the past few decades, several catalytic and other methods for the synthesis of oxazole derivatives have been well documented, such as intramolecular 4 or intermolecular 5 cyclization of acyclic precursors, metal-catalyzed coupling of functionalized oxazoles with suitable reagents, 6 and oxidations of oxazolines, 7 or other relevant protocols.…”

Deciphering Deoxynybomycin Biosynthesis Reveals Fe(II)/α-Ketoglutarate-Dependent Dioxygenase-Catalyzed Oxazoline Ring Formation and Decomposition

“…Oxazoline is a highly significant N-heterocyclic moiety that imparts natural products with a wide range of bioactivities, which is primarily attributed to the nitrogen and oxygen atoms within the five-membered heterocycle to enable strong binding interactions with a variety of enzymes and receptors in biological systems. − For examples, the oxazoline pharmacophore has been incorporated into synthetic drug candidates, such as A-289099 (antitumor), L-161,240 (antibacterial), and etoxazole (commercial pesticide) (Figure A) . Thus, the integration of an oxazoline into bioactive molecules has emerged as an important transformation in organic synthesis. − Oxazoline moieties in natural products are often found as 2-oxazoline, which is mainly derived from serine or threonine residues . In most cases, 2-oxazoline moieties are building blocks in ribosomally synthesized and post-translationally modified peptides (RiPPs) or nonribosomal peptides (NRPs).…”

Copper(i)-catalyzed tandem synthesis of 4,5-functionalized oxazoles from isocyanoacetate and aldehydes

“…Oxazoles are common five-membered nitrogen-containing heterocycles widely found in natural substances and biologically active compounds. 1 For example, martefragin A, which is isolated from Japanese sea algae Martensiafragilis , has potent inhibitory activity against lipid peroxidation, 2 while disorazole A 1 from myxobacterium Sorangiumcellulosum was found to show picomolar antitumor activity by interfering with tubulin polymerization dynamics 3 (Fig. 1).…”