Chemistry and pharmacological diversity of quinoxaline motifs as anticancer agents (original) (raw)
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Design and Synthesis of New Quinoxaline Derivatives as Anticancer Agents and Apoptotic Inducers
Molecules, 2019
The quinoxaline scaffold is a promising platform for the discovery of active chemotherapeutic agents. Three series of quinoxaline derivatives were synthesized and biologically evaluated against three tumor cell lines (HCT116 human colon carcinoma, HepG2, liver hepatocellular carcinoma and MCF-7, human breast adenocarcinoma cell line), in addition to VEGFR-2 enzyme inhibition activity. Compounds VIId, VIIIa, VIIIc, VIIIe and XVa exhibited promising activity against the tested cell lines and weak activity against VEGFR-2. Compound VIIIc induced a significant disruption in the cell cycle profile and cell cycle arrest at the G2/M phase boundary. In further assays, the cytotoxic effect of the highly active compounds was determined using a normal Caucasian fibroblast-like fetal lung cell line (WI-38). Compound VIIIc could be considered as a lead compound that merits further optimization and development as an anti-cancer and an apoptotic inducing candidate against the HCT116 cell line.
Synthesis and in vitro antitumor activity of new quinoxaline derivatives
European journal of medicinal chemistry, 2009
A series of novel 5,7-diamino-3-phenyl-2-benzylamino, 2-phenoxy, and 2-thiophenyl substituted quinoxalines has been designed, synthesized and evaluated for their in vitro antitumor activity towards cell lines of nine different types of human cancers. Some of these compounds exhibited inhibitory effects on the growth of a wide range of cancer cell lines generally at 10(-6) M, in some cases at 10(-7) M and 10(-8) M concentrations. Within this series the benzylamino quinoxaline derivatives 1b-7b were the most active, whereas compound 2c showed the highest MG_MD value (-5.66).
A new and potent class of quinoline derivatives against cancer
Monatshefte für Chemie - Chemical Monthly, 2015
A new class of 4-quinolinylhydrazone derivatives has been synthesized and evaluated for their cytotoxic potential against three cancer cell lines using the MTT assay. Compounds displaying more than 90 % of growth inhibition were evaluated for in vitro anticancer activities against four human cancer cell lines. The results were expressed as the concentrations that induce 50 % inhibition of cell growth (IC 50) in lg/cm 3. These compounds exhibited good cytotoxic activity against at least three cancer cell lines, with IC 50 values between 0.314 and 4.65 lg/ cm 3. These derivatives are useful starting points for further study for new anticancer drugs and confirm the potential of quinoline derivatives as lead compounds in anticancer drug discovery.
Comprehensive review on current developments of quinoline-based anticancer agents
Arabian Journal of Chemistry, 2016
Among heterocyclic compounds, quinoline scaffold has become an important construction motif for the development of new drugs. Quinoline and its derivatives possess many types of biological activities and have been reported to show significant anticancer activity. Quinoline compounds play an important role in anticancer drug development as they have shown excellent results through different mechanism of action such as growth inhibitors by cell cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell migration and modulation. A number of quinoline derivatives have been reported till date for their anticancer activity. The present review, summarizes various mono-, di-, tri-, tetra-and heterocyclic substituent quinoline derivatives with potential anticancer activity. Their mechanism of action and possible structure activity relationship has also been discussed.
Design, synthesis, and docking study of new quinoline derivatives as antitumor agents
Archiv der Pharmazie, 2019
New quinolines substituted with various heterocycles and chalcone moieties were synthesized and evaluated as antitumor agents. All the synthesized compounds were in vitro screened against 60 human cancer cell lines. Compound 13 showed the highest cytotoxicity toward 58 cell lines, exhibiting distinct growth inhibition values (GI 50) against the majority of them, including SR, HL-60 (TB) strains (leukemia), and MDA-MB-435 strains (melanoma), with GI 50 values of 0.232, 0.260, and 0.300 µM, respectively. It exhibited great selectivity toward cancer cell lines, with less toxic effect against normal cells represented by skin fibroblast (BJ) and breast epithelial cell lines (MCF-10F). The enzyme inhibitory activity of compound 13 was evaluated against topoisomerase 1 (Topo 1), epidermal growth factor receptor and vascular endothelial growth factor receptor 2, where it displayed worthy Topo 1 inhibition activity with an IC 50 value of 0.278 µM compared with camptothecin as a reference drug (IC 50 0.224 µM). Docking studies were performed to investigate the recognition profile of compound 13 with the Topo 1 enzyme binding site.
Molecules
Quinoxalines, a class of N-heterocyclic compounds, are important biological agents, and a significant amount of research activity has been directed towards this class. They have several prominent pharmacological effects like antifungal, antibacterial, antiviral, and antimicrobial. Quinoxaline derivatives have diverse therapeutic uses and have become the crucial component in drugs used to treat cancerous cells, AIDS, plant viruses, schizophrenia, certifying them a great future in medicinal chemistry. Due to the current pandemic situation caused by SARS-COVID 19, it has become essential to synthesize drugs to combat deadly pathogens (bacteria, fungi, viruses) for now and near future. Since quinoxalines is an essential moiety to treat infectious diseases, numerous synthetic routes have been developed by researchers, with a prime focus on green chemistry and cost-effective methods. This review paper highlights the various synthetic routes to prepare quinoxaline and its derivatives, cove...
From Molecules to Medicine: The Remarkable Pharmacological Odyssey of Quinoline and It's Derivatives
Oriental journal of chemistry, 2023
Quinoline, a nitrogen-containing heterocyclic molecule, has emerged as an important scaffold in medicinal chemistry due to its diverse pharmacological effects. The fused quinazoline nucleus in particular has garnered attention for its potent properties, including antibacterial, antiviral, anti-cancer, anti-inflammatory, antioxidant, and anticonvulsant effects. The mechanism of action of these quinoline derivatives is specific to their pharmacological activity. Researchers have studied the chemical and pharmacological properties of quinoline derivatives extensively, with a focus on their anticancer activity. Their ability to bind with DNA, impede DNA synthesis, and cause oxidative stress has made them promising candidates for cancer therapy. The quinoline nucleus's unique chemical structure and flexibility of substituents provide a vital component in drug discovery research. This review article provides a comprehensive synthesis of the chemical and pharmacological properties of quinoline derivatives. The study highlights the immense potentiality of this ring system and their pharmacological scaffold. The review covers the diverse biological activity of quinoline derivatives and their mechanism of action, including their effects on DNA synthesis, cell division, virus replication, adhesion to host cells, cytokine generation, gene modulation, free radical scavenging, and neurotransmitter activation. The ability to modify the quinoline nucleus with different substituents around the centroid has made it a privileged scaffold for researchers to work with. Researchers have created novel therapeutic compounds with improved pharmacological characteristics, leading to innovative therapies for various disorders. Further research into synthesis, reactions, and pharmacological effects of quinoline derivatives can pave the way for the development of new drugs. The article specifically focuses on the anticancer activity of quinoline derivatives, highlighting their potential as a viable clinical candidate for cancer therapy. The review emphasizes the importance of the quinoline nucleus as a key scaffold for drug discovery research and encourages further exploration of its chemical and pharmacological properties. In conclusion, this review article provides a comprehensive overview of the immense potential of quinoline derivatives and their significance in medicinal chemistry research.
Discovery of New Quinoxalines as Cytotoxic Agents: Design, Synthesis and Molecular Modeling
Azhar International Journal of Pharmaceutical and Medical Sciences
Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) has played an important role in vascular permeability and cancer angiogenesis. VEGFR-2 inhibitors proved a significant inhibition of cancer propagation. Accordingly, a new series of 6-chloroquinoxalines has been designed and synthesized as inhibitors of VEGFR-2. The antiproliferative effect of the new hits was determined against two cancer cell lines namely; MCF-7 and HCT-116. Remarkably, compound 6 elicited more cytotoxic effect against the above mentioned cell lines with IC50 values 5.11μM and 6.18 μM than doxorubicin (IC50 7.43 μM and IC50 9.27 μM) as reference drug respectively. Moreover, compound 6 proved to be selective to cancer cells rather than human normal cell when examined against WI-38 cell lines. Molecular modeling was studied to proof the binding affinity of our compounds towards VEGFR-2 active site. Furthermore, in silico results showed that, our compounds overcome sunitinib ' s drawbacks; they have no BBB permeation. Particularly, compounds 6 and 9 are not P-glycoprotein (P-gp) substrates as sunitinib.