Synthesis and in vitro evaluation of novel coumarin–chalcone hybrids as potential anticancer agents (original) (raw)
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Development of Some Novel Coumarin-Chalcone Compounds as Anti-proliferative Agents
Journal of Pharmaceutical Research International, 2021
Introduction: Cancer is the world's second leading cause of death and morbidity, behind only heart failure, which claimed the lives of 18.2 million people in 2020. While massive initiatives to establish newer leads and innovative chemotherapeutic methods for combating different types of cancer, continues to be a major concern around the world. As a result, identifying cell-cycle inhibitors and apoptotic triggers to fight cancer cells is an appealing method for finding and developing new anti-tumor drugs. Materials and Methods: The present study involves the rational development and characterization (both physicochemical and spectroscopy) of coumarin-chalcone compounds (A1–A10) and their anti-proliferative potentials against cancer lines of breast cancer origin (MDA-MB468, MDA-MB231, and MCF-7) and non-cancer breast epithelial cell (184B5). Results: The compound A2 exhibited the highest anti-proliferative activity against the cell line MDA-MB-231 as indicated by the GI50 value of...
Chalcone-Coumarin Derivatives as Potential Anti-Cancer Drugs: An in vitro and in vivo Investigation
Anti-Cancer Agents in Medicinal Chemistry, 2013
Cancer cells display an overproduction of reactive oxygen species resulting from an exaggerated intrinsic oxidative stress. However, the concept of deleterious oxidants versus beneficial antioxidants has recently evolved. Indeed, molecules like natural coumarins have shown anti-oxidant or pro-oxidant properties depending on their intracellular concentration. Therefore, we have investigated the structure-activity relationship of a variety of coumarin derivatives in terms of cytotoxicity towards human and murine carcinoma cell lines (HT29, HepG2, A549, MCF7, OVCAR and CT26). Amongst those compounds, (E)-7-methoxy-4-(3-oxo-3phenylprop-1-enyl)-2H-chromen-2-one and (E)-7-hydroxy-4-(3-(4-hydroxyphenyl)-3-oxoprop-1-enyl)-2H-chromen-2-one displayed the most potent cytotoxic effect on colon cancer cells, CT26, (IC50=4.9 M) linked to their pro-oxidant properties. Those compounds triggered the in vitro production of reactive oxygen species by tumor cells, leading to their death through a necrotic process. In vivo, molecules also slowed down tumor growth by 65.7% and 35.4%, respectively, without inducing significant side effects.
2018
Coumarin-chalcone hybrids 3a and 3b were utilized as versatile precursor for the synthesis of coumarinyl-pyridine and coumarinyl-pyrimidine hybrids. The reaction of chalcones 3 with malononitrile or ethyl cyanoacetate proceeded in hot glacial acetic acid and ammonium acetate to afford the coumarinyl 2-aminonicotinonitriles 4 and coumarinyl 2-hydroxynicotinonitriles derivatives 5, respectively. Heating of chalcone derivatives 3 with thiourea in refluxing sodium ethoxide furnished the corresponding coumarinyl-pyrimidines 6. Condensation of coumarinyl-acetohydrazide scaffold 7 various aromatic aldehydes afforded the corresponding acrylohydrazides 8 which underwent heterocyclization with malononitrile furnished the coumarinylpyridinone derivatives 9. The constructed coumarin scaffolds were evaluated in vitro for their anticancer activity via the standard MTT method versus Hepatocellular Carcinoma (HepG2) and breast cancer (MCF-7).
Letters in Drug …, 2011
A series of coumarinyl chalcones derivatives were synthesized and evaluated for their antiproliferative activities on three different breast cancer cell lines (MDA-MB231, MDA-MB468, MCF7) and one non-cancer breast epithelial cell line (184B5). The coumarinyl derivatives exhibited anticancer activity against breast cancer cell lines at a micromolar range. A structure-activity relationship (SAR) analysis was performed by studying the effect of substituents on their antiproliferative activities. One of the compound 3i bearing methoxy substitutions at the R 1 , R 2 and R 3 positions of the phenyl ring showed comparable potency to the reference drug cisplatin as well as a two-fold higher selectivity for the breast cancer cell lines than 184B5 cells.
Recent Strategies for Efficient Synthesis and Biological Activities of Coumarin-Chalcone Derivatives
Asian Journal of Pharmaceutical and Clinical Research, 2020
Coumarins and chalcones are potential pharmacological and biologically active molecules obtained from natural source. Coumarins have predominant pharmacological activities such as antidiabetic, antitumor, and anti-inflammatory activity. Chalcones are also one of the naturally occurring pharmacologically vital molecules with different activities such as anti-inflammatory, antitumor, antimicrobial, and antimalarial activity. Literature reveals that a huge number of coumarinyl chalcone derivatives have various pharmacological activities. Coumarinyl chalcone derivatives gained more prominence due to their significant biological activities. This work explains the current information about synthesis techniques, pharmacological importance, and clinical applications of coumarinyl chalcone derivatives.
Synthesis of coumarin-Chalcone Derivatives
IOSR Journals , 2019
Based on the observed biological activities of Coumarin and chalcones, we have synthesized Coumarin-chalcone hybrids with the aim of evaluating their anti-oxidant properties and Trypanocidal activity against Trypanosoma cruzi, parasite responsible for Chagas disease. All derivatives have been proved to be good anti-oxidants. These preliminary findings encourage us to future structural optimization of these kind of compounds. Various Coumarins were synthesized and converted to Coumarin-Chalcone hybrids. Coumarins were synthesized by treating Salicylaldehyde and Ethyl acetoacetate in presence of piperidine as base and ethanol as solvent. Then Coumarins were converted to Chalcones by reacting with 3-acetyl Coumarin with aldehydes to give Coumarin Chalcone hydrides.
Synthesis and Electrochemical and Biological Studies of Novel Coumarin–Chalcone Hybrid Compounds
Journal of Medicinal Chemistry, 2013
A series of novel hydroxy-coumarin−chalcone hybrid compounds 2a−i has been synthesized by employing a simple and efficient methodology. An electrochemical characterization using cyclic voltammetry and ESR spectroscopy were carried out to characterize the oxidation mechanism for the target compounds. The antioxidant capacity and reactivity were determined by ORAC and ESR assays, respectively. Biological assays were assessed to evaluate the cytotoxicity and cytoprotection capacity against ROS/RNS on BAEC. The results revealed that all tested compounds present ORAC values that are much higher than other well-known antioxidant compounds such as quercetin and catechin. Compound 2e showed the highest ORAC value (14.1) and also presented a low oxidation potential, good scavenging capacity against hydroxyl radicals, low cytotoxicity, and high cytoprotective activity.
Arabian Journal of Chemistry, 2020
Current therapies to treat gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), and other acid-related diseases either prevent stimulation of the parietal cell (H 2-receptor antagonists) or inhibit gastric H ? / K ?-ATPase (proton pump inhibitors). The inhibition of acid production by proton pump inhibitors (PPI's) provides more effective relief of symptoms and healing. A series of novel 4-substituted-2-(1H-benzimidazol-2-yl)methylsulfinylpyrimidines were synthesized as target compounds and antiulcer activity was done using parameters like total acidity, pH, and total gastric acid volume by pylorus ligation method on Wistar rats. Three different dose levels were employed for testings. The target compounds 4-substituted-2-(1H-benzimidazol-2-yl)methylsulfinylpyrimidines were effective for ulcer treatment and among them compounds 10c, 10d, 8b, and 8c exhibited potent antisecretory activity. Overall, compounds 10c, 10d, 8b, and 8c can be looked upon as potential leads for further development and investigations. Keywords Antiulcer agents Á H ? /K ?-ATPase Á Omeprazole Á pH Á Total acidity Á Total gastric acid volume Kishor S. Jain, Vikas K. Raskar contributed equally for the research work.
Journal of Heterocyclic Chemistry, 2018
Various new substituted and fused coumarin analogues have been synthesized via different synthetic pathways. Among which are variable substituted coumarin derivatives bearing either biologically active side chains or rings at 5, 6, and 3 positions of the coumarin nucleus as indicated in compounds 10, 12, 13, 16-19, 21, 23-32, 38, and 42-45. In addition, different pyranocoumarin derivatives either substituted as in compounds 2, 3, and 6 or fused as compounds 33-36, pyranoxanthene analogues such as compounds 4 and 46, coumarinotriazolothiadiazine derivative 8, coumarinonaphthodiazocin analogue 39 and coumarinopyrazolone derivative 40 were synthesized. Thirty-eight of the synthesized compounds were subjected to in vitro anticancer screening against mammalian liver carcinoma HepG2 and breast carcinoma MCF7 cell lines using Cisplatin as a standard reference. The anticancer activity screening results revealed that, among the tested compounds, compounds 16, 40, and 43 bearing 4-chlorophenyl-2-aminopyridine-3carbonitrile attached to C 6 position, fused pyrazolone ring or attached to 4-chlorophenyl-2-oxodihydropyridine-3-carbonitrile at C 3 position of the coumarin nucleus, respectively, exhibited moderate to strong activity against both cell lines.