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

2021 ◽  
Vol 21 ◽  
Author(s):  
Swanand Kulkarni ◽  
Kamalpreet Kaur ◽  
Vikas Jaitak
Keyword(s):  
Protein Kinases ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Rational Design ◽  
New Drugs ◽  
Synthetic Methods ◽  
Mitochondrial Enzymes ◽  
Sar Studies ◽  
G Quadruplex ◽  
Oxazole Derivatives

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.

scholarly journals MN4-based G4-Ligands as Potential Antitumor Agents: A Review

2021 ◽  
Vol 12 (3) ◽  
pp. 3977-3988
Keyword(s):  
Metal Complexes ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Genomic Dna ◽  
Rational Design ◽  
Structural Engineering ◽  
Antitumor Agents ◽  
Medical Field ◽  
G Quadruplex ◽  
Potential Antitumor

Cisplatin-based metal drugs have been widely used clinically as anticancer agents. However, these drugs also harm ordinary tissues because cisplatin kills cancer cells by attacking genomic DNA. Therefore, it has been shown that cisplatin-based metal drugs have some serious side effects that cannot be avoided. In order to replace the target site of genomic DNA, G-quadruplex nucleic acid is considered to be an alternative and attractive target for anticancer agents because G-quadruplex always folds into a parallel topology and is, therefore, more important than DNA. This review discussed the recent advancements in the rational design and the development of metal complexes containing anticancer drugs to interact and stabilize or cleave the G4 structure selectively. Further, we also highlighted the G4-interacting transition metal complexes, interacting modes, and their potentials to serve as anticancer drugs in the medical field. The significance of this survey lies in designing the metallodrugs from the most fundamental characteristic of electronic structural engineering to an increasingly reasonable dimension of bio-science.

QSAR Studies to Predict Activity of HSP90 Inhibitors

2021 ◽  
Vol 21 ◽  
Author(s):  
Vaishali M. Patil ◽  
Neeraj Masand ◽  
Satya P. Gupta ◽  
Brian S. J. Blagg
Keyword(s):  
Anticancer Agents ◽  
Heat Shock Protein 90 ◽  
New Drugs ◽  
Signaling Proteins ◽  
Hsp90 Inhibitors ◽  
Oncogenic Signaling ◽  
Qsar Studies ◽  
Sar Studies ◽  
Promising Target ◽  
Qsar Models

: Heat shock protein 90 (HSP90) is a multichaperone complex that mediates the maturation and stability of a variety of oncogenic signaling proteins. HSP90 has emerged as a promising target for the development of anticancer agents. Heterocyclic chemical moieties with HSP90 inhibitory activity were studied continuously during the last decades, and resulting data were applied by medicinal chemists to design and develop new drugs. Their structure-activity relationship (SAR) studies and QSAR models have been derived to assist the current drug development process. The QSAR models are obtained via multiple linear regression (MLR) and non-linear approaches. Interpretation of the reported model highlights the core template required to design novel, potent HSP90 inhibitors to be used as anticancer agents.

scholarly journals Synthetic Strategies of Pyrimidine-Based Scaffolds as Aurora Kinase and Polo-like Kinase Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5170
Author(s):  
Mrunal Jadhav ◽  
Kaksha Sankhe ◽  
Richie R. Bhandare ◽  
Zehra Edis ◽  
Samir Haj Bloukh ◽  
...  
Keyword(s):  
Small Molecules ◽  
Protein Kinases ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Antitumor Agents ◽  
Aurora Kinase ◽  
Pyrimidine Ring ◽  
Pyrimidine Derivatives ◽  
Comprehensive Overview

The past few decades have witnessed significant progress in anticancer drug discovery. Small molecules containing heterocyclic moieties have attracted considerable interest for designing new antitumor agents. Of these, the pyrimidine ring system is found in multitude of drug structures, and being the building unit of DNA and RNA makes it an attractive scaffold for the design and development of anticancer drugs. Currently, 22 pyrimidine-containing entities are approved for clinical use as anticancer drugs by the FDA. An exhaustive literature search indicates several publications and more than 59 patents from the year 2009 onwards on pyrimidine derivatives exhibiting potent antiproliferative activity. These pyrimidine derivatives exert their activity via diverse mechanisms, one of them being inhibition of protein kinases. Aurora kinase (AURK) and polo-like kinase (PLK) are protein kinases involved in the regulation of the cell cycle. Within the numerous pyrimidine-based small molecules developed as anticancer agents, this review focuses on the pyrimidine fused heterocyclic compounds modulating the AURK and PLK proteins in different phases of clinical trials as anticancer agents. This article aims to provide a comprehensive overview of synthetic strategies for the preparation of pyrimidine derivatives and their associated biological activity on AURK/PLK. It will also present an overview of the synthesis of the heterocyclic-2-aminopyrimidine, 4-aminopyrimidine and 2,4-diaminopyrimidine scaffolds, and one of the pharmacophores in AURK/PLK inhibitors is described systematically.

Potential Role of In vitro-In vivo Correlations (IVIVC) for the Development of Plant Derived Anticancer Drugs

2020 ◽  
Vol 21 ◽  
Author(s):  
A.Mohamed Sheik Tharik ◽  
S.B. Santhosh ◽  
Murugesan Susitra Manjari ◽  
S.N. Meyyanathan
Keyword(s):  
Natural Products ◽  
Anticancer Drugs ◽  
Internal Control ◽  
Anticancer Agents ◽  
Scale Up ◽  
Primary Source ◽  
New Drugs

Background: Conventional medicines, along with herbal formulations of Chinese, serves as the primary source and hub of active new drugs where the initial research concentrate in the extraction and isolation of bioactive lead com-pound(s) to treat several diseases largely for cancer. Plant-derived natural products and their analogs reveal a significant source of several clinically useful anticancer agents. Herbs and herbal derived active compounds play an unavoidable role in the treatment, drug discovery and delivery for decades,as evidenced by numerous existing marked drugs and various cancer-related molecular targets in clinical development. Objective: Solubility, resistance and metabolic limitations of the drugcan be overcome by suitable molecular modifications; Due to enhancements in tumor targeting technology, some agents which failed in earlier clinical studies are also stimulating renewed interest. In this connection, In Vitro In Vivo Correlation (IVIVC) plays an important role in the development of dosage forms in the field of pharmaceutical technology. Conclusion: IVIVC tool fastens and improves the drug development process and product quality, which is also utilized in internal control for scale-up, to improve formulations and alternativeproduction processes. Most importantly, this IVIVC tool lessens the quantity of human studies during new pharmaceuticals developments. In this review, we would like to grab the attention of readers to the importance and significance of IVIVC for natural products of anticancer drugs examples such as Docetaxel, Etoposide phosphate, 6-Gingerol, Capsaicin, etc.

β-Lactone derivatives and their anticancer activities: A short review

2021 ◽  
Vol 21 ◽  
Author(s):  
Jun Wang ◽  
Yumin Shi ◽  
Dan Jiang
Keyword(s):  
Drug Resistance ◽  
Anticancer Agents ◽  
Rational Design ◽  
Genetic Diseases ◽  
Short Review ◽  
New Drugs ◽  
Anticancer Activities ◽  
Naturally Occurring ◽  
Body Tissues ◽  
Privileged Structures

: Cancers, a set of genetic diseases that can change the behavior and cell growth in body tissues, are the second leading cause of death accross the world. Several treatment approaches such as radiation, immunotherapy and chemotherapy can be applied to cure cancer, and among them, chemotherapy is one of the primary treatments for cancer, in which chemotherapeutic drugs are used. Great achievements have been made in the development of novel anticancer agents, but drug resistance is usually generated quickly, making overcoming drug resistance or developing more effective anticancer agents an imperative challenge. β-Lactones (2-oxetanones) are chemically diverse and often referred as privileged structures for the discovery of new drugs including anticancer agents. Marizomib (Salinosporamide A), a naturally occurring β-lactone proteasome inhibitor derived from the marine actinobacterium Salinispora tropica, has been termed as orphan drug against multiple myeloma. Therefore, β-lactones are useful scaffolds for the discovery of novel anticancer agents. This review is an endeavour to highlight the advances in β-lactone derivatives with anticancer potential, and the synthetic strategies, structure-activity relationships as well as modes of action are also discussed to pave the way for further rational design.

Natural compounds from Juncus plants interacting with telomeric and oncogene G-quadruplex structures as potential anticancer agents

2021 ◽  
Author(s):  
Chiara Platella ◽  
Domenica Capasso ◽  
Claudia Riccardi ◽  
Domenica Musumeci ◽  
Marina DellaGreca ◽  
...  
Keyword(s):  
Side Effects ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Natural Compounds ◽  
G Quadruplex

Aiming at discovering novel, putative anticancer drugs featured by low-to-null side effects, natural compounds isolated from Juncaceae were here studied in their ability to target G-quadruplex structures originated from cancer-related...

Biological Activity of Trans-Membrane Anion Carriers

2018 ◽  
Vol 25 (30) ◽  
pp. 3560-3576 ◽  
Author(s):  
Massimo Tosolini ◽  
Paolo Pengo ◽  
Paolo Tecilla
Keyword(s):  
Biological Activity ◽  
Membrane Transport ◽  
Anticancer Agents ◽  
Biological Effects ◽  
Structure Activity Relationship ◽  
New Drugs ◽  
Activity Relationship ◽  
Anion Channels ◽  
Cellular Homeostasis ◽  
Structure Activity

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels.

Oxazole-Based Compounds As Anticancer Agents

2020 ◽  
Vol 26 (41) ◽  
pp. 7337-7371 ◽  
Author(s):  
Maria A. Chiacchio ◽  
Giuseppe Lanza ◽  
Ugo Chiacchio ◽  
Salvatore V. Giofrè ◽  
Roberto Romeo ◽  
...  
Keyword(s):  
Cancer Research ◽  
Drug Discovery ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Chemical Diversity ◽  
Biologically Active ◽  
New Drugs ◽  
The Core ◽  
Anti Cancer ◽  
Biologically Active Derivatives

: Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

Recent Design and Structure-Activity Relationship Studies on Modifications of DHFR Inhibitors as Anticancer Agents

2019 ◽  
Vol 26 ◽  
Author(s):  
Agnieszka Wróbel ◽  
Danuta Drozdowska
Keyword(s):  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Physicochemical Characterization ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Biological Research ◽  
Structure Activity ◽  
Dhfr Inhibitors

Background: Dihydrofolate reductase (DHFR) has been known for decades as a molecular target for antibacterial, antifungal and anti-malarial treatments. This enzyme is becoming increasingly important in the design of new anticancer drugs, which is confirmed by numerous studies including modelling, synthesis and in vitro biological research. This review aims to present and discuss some remarkable recent advances on the research of new DHFR inhibitors with potential anticancer activity. Methods: The scientific literature of the last decade on the different types of DHFR inhibitors has been searched. The studies on design, synthesis and investigation structure-activity relationship were summarized and divided into several subsections depending on the leading molecule and its structural modification. Various methods of synthesis, potential anticancer activity and possible practical applications as DHFR inhibitors of new chemical compounds were described and discussed. <p> Results: This review presents the current state of knowledge on the modification of known DHFR inhibitors and the structures and searching for over eighty new molecules, designed as potential anticancer drugs. In addition, DHFR inhibitors acting on thymidylate synthase (TS), carbon anhydrase (CA) and even DNA-binding are presented in this paper. <p> Conclusion: Thorough physicochemical characterization and biological investigations it is possible to understand structure-activity relationship of DHFR inhibitors. This will enable even better design and synthesis of active compounds, which would have the expected mechanism of action and the desired activity.

Phytosterols and Triterpenoids for Prevention and Treatment of Metabolic-related Liver Diseases and Hepatocellular Carcinoma

2019 ◽  
Vol 20 (3) ◽  
pp. 197-214 ◽  
Author(s):  
Isabel Sánchez-Crisóstomo ◽  
Eduardo Fernández-Martínez ◽  
Raquel Cariño-Cortés ◽  
Gabriel Betanzos-Cabrera ◽  
Rosa A. Bobadilla-Lugo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Anticancer Agents ◽  
Liver Diseases ◽  
Membrane Receptors ◽  
New Drugs ◽  
Sexual Hormones ◽  
Steroid Nucleus ◽  
Alcoholic Fatty Liver ◽  
Prevention And Treatment

Background: Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs. Review and Conclusion: Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.

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