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.

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 G-quadruplex DNA targeted metal complexes acting as potential anticancer drugs

2017 ◽  
Vol 4 (1) ◽  
pp. 10-32 ◽  
Author(s):  
Qian Cao ◽  
Yi Li ◽  
Eva Freisinger ◽  
Peter Z. Qin ◽  
Roland K. O. Sigel ◽  
...  
Keyword(s):  
Metal Complexes ◽  
Anticancer Drugs ◽  
Quadruplex Dna ◽  
G4 Dna ◽  
G Quadruplex

This review summarizes the recent development of G4 DNA targeted metal complexes and discusses their potential as anticancer drugs.

Recent Progress and Future Potential for Metal Complexes as Anticancer Drugs Targeting G-quadruplex DNA

2012 ◽  
Vol 19 (18) ◽  
pp. 2957-2975 ◽  
Author(s):  
J. Zhang ◽  
F. Zhang ◽  
H. Li ◽  
C. Liu ◽  
J. Xia ◽  
...  
Keyword(s):  
Metal Complexes ◽  
Anticancer Drugs ◽  
Recent Progress ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Future Potential

scholarly journals Toxic Effects of Metallopharmaceuticals

2017 ◽  
Vol 18 (3) ◽  
pp. 191-194 ◽  
Author(s):  
Slobodan Novokmet ◽  
Isidora Stojic ◽  
Katarina Radonjic ◽  
Maja Savic ◽  
Jovana Jeremic
Keyword(s):  
Metal Complexes ◽  
Transition Metal Complexes ◽  
Anticancer Agents ◽  
Rational Design ◽  
Current Knowledge ◽  
The Past ◽  
Ru Complexes ◽  
Key Features

Abstract Discovery of the metallopharmaceutical cisplatin and its use in antitumour therapy has initiated the rational design and screening of metal-based anticancer agents as potential chemotherapeutics. In addition to the achievements of cisplatin and its therapeutic analogues, there are significant drawbacks to its use: resistance and toxicity. Over the past four decades, numerous transition metal complexes have been synthesized and investigated in vitro and in vivo. The most studied metals among these complexes are platinum and ruthenium. The key features of these investigations is to find novel metal complexes that could potentially exert less toxicity and equal or higher antitumour potency and to overcome other pharmacological deficiencies. Ru complexes have a different mode of action than cisplatin does, some of which are under clinical trials for treating metastatic or cisplatin-resistant tumours. This review consists of the current knowledge, published and unpublished, related to the toxicity of metallopharmaceuticals, and special attention is given to platinum [Pt(II) and Pt(IV)] and ruthenium [Ru(II) and Ru(III)] complexes.

Screening Potential Antitumor Agents from Natural Plant Extracts by G-Quadruplex Recognition and NMR Methods

2008 ◽  
Vol 120 (30) ◽  
pp. 5672-5674 ◽  
Author(s):  
Qiuju Zhou ◽  
Lin Li ◽  
Junfeng Xiang ◽  
Yalin Tang ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Plant Extracts ◽  
Antitumor Agents ◽  
Natural Plant ◽  
G Quadruplex ◽  
Nmr Methods ◽  
Potential Antitumor

Metal Complexes of Natural Product Like-compounds with Antitumor Activity

2019 ◽  
Vol 19 (1) ◽  
pp. 48-65 ◽  
Author(s):  
Beatriz L. Heras ◽  
Ángel Amesty ◽  
Ana Estévez-Braun ◽  
Sonsoles Hortelano
Keyword(s):  
Metal Complexes ◽  
Natural Product ◽  
Active Sites ◽  
Rational Design ◽  
Complex Disease ◽  
Antitumor Agents ◽  
Research Activity ◽  
Drug Molecules ◽  
Starting Point ◽  
Negative Side Effects

Cancer continues to be one of the major causes of death worldwide. Despite many advances in the understanding of this complex disease, new approaches are needed to improve the efficacy of current therapeutic treatments against aggressive tumors. Natural products are one of the most consistently successful sources of drug leads. In recent decades, research activity into the clinical potential of this class of compounds in cancer has increased. Furthermore, a highly promising field is the use of metals and their complexes in the design and development of metal-based drugs for the treatment of cancer. Metal complexes offer unique opportunities due to their ability to alter pharmacology, improving the efficacy and/or reducing the negative side effects of drug molecules. In addition, transition metals as copper, iron, and manganese, among others, can interact with active sites of enzymes, playing important roles in multiple biological processes. Thus, these complexes not only possess higher activities but also reach their targets more efficiently. This review article highlights recent advances on the emerging and expanding field of metal-based drugs. The emphasis is on new therapeutic strategies consisting of metal complexes with natural product like-compounds as a starting point for the rational design of new antitumor 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.

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