Synthesis of coumarin heterocyclic derivatives with antioxidant activity and in vitro cytotoxic activity against tumour cells (original) (raw)
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SYNTHESIS, REACTIVITY, ANTI-OXIDANT AND CYTOTOXICITY EVALUATION OF SOME COUMARIN DERIVATIVES
EUROPEAN JOURNAL OF PHARMACEUTICAL AND MEDICAL RESEARCH, 2018
In the present work 3-amino-8-methoxy coumarin was prepared either by microwave irradiation or by convential method. It was used as a key starting material for the synthesis of triazole thione (8), Schiffs’ bases (10), thiazolone (11a-d), pyrimidinethione (13), aminothiazole (15) and isoxazole (18) derivatives through its reaction with different reagents. The structures of the newly synthesized compounds were elucidated on the basis of their elemental analysis and by using different spectroscopic methods. The free radical scavenging activity of some newly synthesized derivatives was determined by measuring their interaction with the stable free radical DPPH and some compounds have shown encouraging antioxidant activity. Also, they were screened for their in-vitro cytotoxicity against two human cancer cell lines namely HEIA cells (human cervical carcinoma) and A-549 cells (human lung cancer cell line). The IC50 values (the sample concentration that produces 50% reduction in cell growth) in μg/mL showed that some of the tested compounds exhibited significant cytotoxic effect.
Medicinal Chemistry Research, 2015
A series of novel (Z)-3-(2-(4-(2-oxo-2H-chromen-3-yl) thiazol-2-yl-)hydrazono)indolin-2-one (8a–8d, 9)were synthesized with various substituted indole derivatives. Structures of the newly synthesized compounds were elucidated by FT-IR, 1H NMR, 13C NMR and API-ES mass spectral data. In vitro evaluation of these coumarin compounds revealed cytotoxicity from 6.2 to 18 lg/mL against CEM, 8.2 to 21 lg/mL against L1210, 09 to 19 lg/mL against molt 4/C8, 8.6 to 12 lg/mL against HL60 and 8 to 16 lg/mL against BEL7402. The antioxidant activity of the synthesized compounds was evaluated by DPPH scavenging method. Compounds 8c, 8d and 9 showed significant antioxidant activity compared with that of standard drug ascorbic acid.
Asian Journal of Research in Biochemistry, 2019
Background: Coumarin and thiazole derivatives have been used traditionally for many centuries. Because they have anti-tumor, antioxidant activities, and induced apoptosis. Aim: The present study aims to investigate the in vivo antitumor, and antioxidant activities of potassium salt of 5-(4-chlorophenyl)-2-[(7-hydroxy coumarin-3-ylethylidene) acetyl hydrazine]-1,3 thiazole (5a) and 5-(4-chlorophenyl)-2-[(8-hydroxy coumarin-3-ylethylidene) acetyl hydrazine]-1,3 thiazole (5b). Materials and Methods: Toxicity has been determined for the synthesized compound. Anti-cancer and anti-oxidant activities were studied through the evaluation of tumor cell viability, lifespan prolongation and antioxidant estimation. Results: Doses of up to 500 mg/kg showed good protection in 5a and 5b compounds. Results of in vivo anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells for the compounds studied showed a significant reduction in the volume and number of ascites. And increased in life span. In therapeutic and preventive groups, compounds 5a and 5b have anti-oxidant properties by a
Synthesis and Antioxidant Evaluation of Some New 3-Substituted Coumarins
Archiv der Pharmazie, 2011
3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of 2-aminothiazole derivative 3 via bromination of 1 to afford acetylbromide 2 followed by treatment with thiourea or via Biginelli reaction of 1. Treatment of 3 with 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, 2-methyl-4H-benzo[d] [1,oxazin-4-one, furo[3,4-b]pyrazine-5,7-dione or 2-methyl-5,6,7,8-tetrahydro-4Hbenzothieno[2,3-d][1,3]oxazin-4-one afforded diazine derivatives 4-7. Also, pyridopyrimidine 8 was obtained via a one pot reaction of 6-aminothiouracil, p-chlorobenzaldehyde and 3-acetylcoumarin. Moreover, refluxing of 6-aminothiouracil with one equivalent amount of 2 afforded the thiazolopyrimidine 9, while the pyrrolothiazolopyrimidine 10 was revealed when two equivalent amounts of 2 was used. Furthermore, treatment of enamine 11 with 2-aminobenzothiazole or 6-aminothiouracil afforded the pyrimidine derivatives 12 and 13, respectively. Transamination of enamine 11 with m-anisidine followed by cyclization of the resulting enaminone 14 gave the desired quinoline 15. Also, treatment of 11 with thiophenol in dioxane gave the mercapto derivative 16. Moreover, coupling of 11 with 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl-diazonium chloride, followed by complete cyclization of the resulting product afforded the pyridopyrazolothiazine 19 via the intermediate 18. Furthermore, the pyrazolopyrimidine 20 was revealed via a one pot condensation of 11, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and ammonium acetate. The thiadiazine derivatives 21-23 were obtained via treatment of 2 with the corresponding o-aminothiols. Desulphonation of 23 afforded the pyrazolotriazine 24. Finally, reaction of 2 with 2-hydroxybenzaldehyde gave benzofuran derivative 25. Representative compounds of the synthesized products were evaluated as antioxidant agents.
Russian Journal of Bioorganic Chemistry, 2017
A series of semicarbazones, thiocarbazones, 1,3,4-oxadiazoles, and 1,3,4-thiadiazoles bearing coumarin and pyrazole moiety have been synthesized. The new synthesized compounds were screened in vitro for their antimicrobial and antioxidant activities. Preliminary studies showed that among the synthesized new compounds, chloro-substituted thiosemicarbazone showed excellent activities against all tested organisms; at the same time, methyl substituted thiosemicarbazone showed greater activity against E. coli. Chloro-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole demonstrated greater DPPH and hydroxyl radical scavenging abilities. Molecular docking studies indicate that 1,3,4-oxadiazoles and 1,3,4-thiadiazoles manifest better interaction with CAT (catalase) and GPx (glutathione peroxidase) than that with SOD (superoxide dismutase). Studies on the antimicrobial and antioxidant activities of the synthesized compounds compared with those of their starting compounds are discussed.
Synthesis and Antioxidant Activity of Some New Coumarinyl- 1, 3-Thiazolidine-4-ones
A series of Schiff’s bases (E)-N-2-aryliden-2-(4-methyl-2-oxo-2H-chromen-7- yloxy)acetohydrazides 2a-l and N-(2-(substituted phenyl)-4-oxo-thiazolidin-3-yl)-2-(4- methyl-2-oxo-2H-chromen-7-yloxy)acetamides 3a-l were synthesized and evaluated for their antioxidant activity by the phosphomolybdenum method. Most of the Schiff’s bases and thiazolidine-4-ones bearing two hydroxyl groups on the phenyl ring showed excellent antioxidant activity in comparison with ascorbic acid. Preliminary investigation on cytotoxic and antifungal activity was done on some representative samples.
Synthesis and Evaluation of New Coumarins as Antitumor and Antioxidant Applicants
Journal of Medicinal and Chemical Sciences, 2022
This work involves the synthesis of eight novel fused coumarin compounds, which were confirmed by various spectrophotometers and then, assessed for their apoptotic-inducing and free radical-quenching activities. The pharmacokinetic parameters were evaluated in silico using pre-ADMET, a free online program. The apoptotic-inducing activity was tested against six tumorigenic cell lines. Also, their safety against normal cells was examined. The free radical-quenching activity was assessed by checking these compounds' ability to eliminate DDPT and hydroxyl moieties. Pharmacokinetic investigations showed that the synthesized fused coumarin compounds have excellent penetration across the GIT mucosa and most of them have poor penetration across the blood-brain barrier. These findings suggest good oral bioavailability along with low neurological toxicity profiles. The evaluation of the apoptotic-inducing activity revealed that all of the compounds have weaker activity as compared to the reference. Among these compounds, SA4 was the most potent one. Nevertheless, all of these new compounds had an excellent safety profile against normal cells. On the other hand, the assessment of the free radical-quenching activity of these synthesized compounds also indicated that all of them were less active than the reference. In this field, SA0 was the strongest free radical-quenching compound. From these realizations, along with the apparent safety and good pharmacokinetic characteristics in accordance with the in silico study, compounds SA4 and SA0 are considered the most promising agents. The authors hope that these new fused coumarin compounds can be utilized in the coming years for the production of new powerful drugs with apoptoticinducing and free radical-quenching potentials which can help in the battle against many diseases.
Molecules (Basel, Switzerland), 2016
Coumarins are naturally occurring oxygen heterocyclic compounds having multifarious medicinal properties, hence used as lead compounds for designing new potent analogs. The chromene butenoic acid 3 and the benzochromene butenoic acid 4 which are derived from the reaction of glyoxalic acid with 3-acetylcoumarin and 3-acetylbenzocoumarin, respectively, were reacted with different nitrogen and carbon nucleophiles to give new heterocyclic compounds. The structures of the prepared compounds were elucidated by IR, ¹H-NMR, and mass spectroscopy. Some of the newly prepared compounds were tested in vitro against a panel of four human tumor cell lines namely; hepatocellular carcinoma (liver) HepG2, colon cancer HCT-116, human prostate cancer PC3, and mammary gland breast MCF-7. Also they were tested as antioxidants. Almost all of the tested compounds showed satisfactory activity.