Antiproliferative, DNA cleavage, and ADMET study of substituted 2-(1-benzofuran-2-yl) quinoline-4-carboxylic acid and its esters

Anantacharya, R.; Manjulatha, K.; Satyanarayan, N. D.; Santoshkumar, S.; Kaviraj, M. Y.

doi:10.1080/23312009.2016.1158382

Cited by 16 publications

(11 citation statements)

References 25 publications

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“…In continuation of search on new compounds for antiproliferation treatment from our laboratory [28][29][30][31][32], we discovered that 2-(1-benzofuron-2-yl) quinoline-4-carboxylic acid and its esters [28] and 2-(benzofuran-2-yl)-4-(5-phenyl-4H-1,2,4-triazol-3-yl) quinoline and its derivatives [29] have possessed appreciable cytotoxic properties. Hence, the present work deals with the synthesis and antiproliferative potential of 4-(piperidin-1-ylmethyl)-2-(thiophen-2-yl) quinoline and its derivatives, along with detailed in silico pharmacokinetic and druglikeness properties Scheme 1.…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative and in Silico Admet Study of New 4-(Piperidin-1-Ylmethyl)-2- (Thiophen-2-Yl) Quinoline Analogues

Harishkumar

2018

Asian J Pharm Clin Res

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Objective: Synthesis and antiproliferative study of novel 4-(piperidin-1-ylmethyl)-2-(thiophen-2-yl) quinoline 7(a-j) derivatives.Methods: 4-(piperidin-1-ylmethyl)-2-(thiophen-2-yl) quinolines were synthesized by the addition of 4-(chloromethyl)-2-(thiophen-2-yl) quinoline (0.01 mol), piperidine (0.01 mol) in DMF (10 v) and K 2 CO 3 ( 0.02 mol). The anticancer activity of the title compounds performed against T-47D, HeLa, HepG2, and MCF-7 human cancer cell lines growth was investigated by MTT assay. Results:The compounds 7b and 7g exhibited 90% of the growth inhibitory effect on T-47D, HeLa, and MCF-7 and also 80% growth inhibition in HepG2 when compared with standard drug paclitaxel. Conclusion:The synthesized compounds 4-(piperidin-1-ylmethyl)-2-(thiophen-2-yl) quinoline 7(a-j) exhibited a considerable degree of growth inhibition of human cancer cell lines. The synthesized molecules 7(a-j) are in acceptable range and are less toxic and can be considered as possible hits for drug discovery.In continuation of search on new compounds for antiproliferation treatment from our laboratory [28][29][30][31][32], we discovered that 2-(1-benzofuron-2-yl) quinoline-4-carboxylic acid and its esters [28] and 2-(benzofuran-2-yl)-4-(5-phenyl-4H-1,2,4-triazol-3-yl) quinoline and its derivatives [29] have possessed appreciable cytotoxic properties. Hence, the present work deals with the synthesis and antiproliferative potential of 4-(piperidin-1-ylmethyl)-2-(thiophen-2-yl) quinoline and its derivatives, along with detailed in silico pharmacokinetic and druglikeness properties Scheme 1. METHODS MaterialsCommercially available chemicals are used in the synthesis of compounds 7(a-j). The compounds were purified by column chromatography using silica gel 100-200 mesh with occasional monitoring by pre-coated aluminum thin layer chromatography (TLC) plates procured from Merck. Melting points were recorded by the open capillary method and are uncorrected by Raga Melting Point Apparatus. The 1 H-nuclear magnetic resonance (NMR) and 13 C-NMR spectra were recorded on a 400 MHz and 100 MHz, Bruker spectrometer using CDCl 3 as solvent and TMS as an internal standard. Mass spectra were recorded on the liquid chromatography-mass spectrometry Agilent mass spectrometer. Method 2-(1-thiophene-2-yl)quinoline-4-carboxylic acid 3(a-b)Isatin 1(a-b) (0.01 mol) and ethanol (10 v) were taken in a round bottom flask, to this 33% aq. KOH was added dropwise at 0-5°C followed by addition of 2-acetylthiophene 2 (0.01 mol). The reaction was refluxed at 75°C for 8 h. After completion, the reaction mixture was neutralized with dilute HCl. The precipitate, thus, formed was filtered, washed with ethyl acetate to remove impurities and dried to get compound 3(a-b). Methyl 2-(1-thiophene-2-yl) quinolone-4-carboxylates 4(a-b)2-(1-thiophene-2-yl) quinoline-4-carboxylic acid 3(a-b) (0.01 mol) was taken in methanol (10 v) in a round bottom flask, to this two drops of Conc. H 2 SO 4 was added. The reaction was refluxed at 75°C for 8 h. After completion, the reaction mixt...

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Section: Discussionmentioning

confidence: 99%

Antiproliferative and in Silico Admet Study of New 4-(Piperidin-1-Ylmethyl)-2- (Thiophen-2-Yl) Quinoline Analogues

Harishkumar

2018

Asian J Pharm Clin Res

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“…Literature survey revealed that chemotherapeutic agents, such as vorozole, letrozole and anastrozole consisting of substituted 1, 2, 4-triazole ring, are presently being used in the treatment of breast cancer [7], additionally 1, 2, 4 triazole derivatives have been reported to inhibit enzymes responsible for the expression of tumors such as aromatase [8] and tubulin polymerase [9]. Keeping in view of the above-mentioned facts, and in continuation of our research on coupled heterocycles [10,11], for biological evaluation, we focused on the synthesis of structurally distinct novel 2-(1-benzofuran-2-yl)-4-(5-phenyl-4H-1, 2, 4-triazol-3-yl) quinoline derivatives 3(a-m), for in vitro antiproliferative study on different cancer cell lines viz. MCF-7 (breast cancer), K562 (leukemic cancer), HeLa (cervical cancer), Colo205 (colorectal adenocarcinoma) and HepG2 (Hepatocellular carcinoma) by MTT assay [11,12].…”

Section: Introductionmentioning

confidence: 97%

Antiproliferative, Adme and Potential in Silico G6pdh Inhibitory Activity of Novel 2-(1-Benzofuran-2-Yl)-4-(5-Phenyl-4h-1, 2, 4-Triazol-3-Yl) Quinoline Derivatives

Santoshkumar

Manjulatha

Satyanarayan

et al. 2016

Int J Pharm Pharm Sci

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Objectives: Synthesis of new 2-(1-benzofuran-2-yl)-4-(5-phenyl-4H-1, 2, 4-triazol-3-yl) quinoline and its derivatives for antiproliferative potential against cancer cells.Methods: The general methods were employed for the synthesis and the structures were confirmed by IR, 1H-NMR, 13C-NMR and mass spectral analysis. The antiproliferative activity was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and molecular docking study were performed by Auto Dock Tools. In silico Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) study for the drug, likeliness was carried out on ACD/lab-2.Results: The compound 3l showed 44, 44, 38 and 37 % inhibition against MCF-7, HepG2, Colo205 and HeLa cell lines, respectively; whereas, the compounds 3i and 3j exhibited 49 and 42 % inhibition against MCF-7 cell line. The molecular docking study revealed that the compound 3i has the lowest binding energy (-8.60 Kcal mol-1), suggesting to be potentially best inhibitor of Glucose-6-phosphate dehydrogenase (G6PDH). The in silico ADME analysis also revealed that compound 3i does not violate any of the Lipinski rules of five and has the best stimulative human colonic absorption up to 95 %.Conclusion: The study reveals that the compounds containing benzofuran coupled nitrogen heterocycles are essential for activity as they possess excellent drug-like characteristics.

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“…The samples were dissolved in DMSO (DMSO; not exceeding the final concentration of 0.01%) and further diluted in cell culture medium. The antiproliferative response of the extract was assessed by MTT assay [3-(4, 5-dimethylthiazole-2yl) -2, 5-diphenyltetrazolium bromide] [31]. Cells (∼10,000) were plated in 200 µl growth medium in the presence or absence of the extract (25, 50, 100, and 200 µg/ml) in 96-well culture plates for 24 hrs.…”

Section: Antiproliferative Activity By Mtt Assaymentioning

confidence: 99%

Antiproliferative and Dna Cleavage Activity of Various Solvent Extracts of Acacia Farnesiana Linn. Pod

Manjulatha

2017

Asian J Pharm Clin Res

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Objective: Cancer has become the major disease by uncontrolled cell growth effecting large population on the globe. This study, deals with antiproliferative activity of different solvent extracts, viz., n-hexane (S 1 ), dichloromethane (DCM) (S 2 ), and methanol (S 3 ) of Acacia farnesiana pod on four cancer cell lines, viz., chronic myelogenous leukemia (K562), breast cancer (MCF-7), hepatocellular carcinoma (HePG2), colorectal adenocarcinoma (Colo 205), and DNA cleavage activity of the extracts on CT-DNA. Methods:The antiproliferative study was performed by MTT assay and DNA cleavage studies of the solvent extracts (S 1 , S 2 , and S 3 ) and its fractions (S 4 and S 5 ) was carried out by agarose gel electrophoresis method. Results:The antiproliferative activity results revealed that n-hexane extract (S 1 ) has showed activity against MCF-7 (21.70 %) cell line and methanol extract (S 3 ) against K562 (24.5%) and HePG2 (23.3%) cell lines. The DNA cleavage could be seen at every concentration tested by n-hexane (S 1 ), DCM (S 2 ), and methanol (S 3 ) extracts and significant cleavage was observed at concentrations of 25, 50, and 100 µg by fractions (S 4 ) and (S 5 ) of methanol extract. Conclusion:The results indicated that the extract of A. farnesiana pod (n-hexane and methanol) has antiproliferative properties and the DNA cleavage studies performed on CT-DNA was found that the extracts and its fractions showed significant activity at the concentrations tested.

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Antiproliferative, DNA cleavage, and ADMET study of substituted 2-(1-benzofuran-2-yl) quinoline-4-carboxylic acid and its esters

Cited by 16 publications

References 25 publications

Antiproliferative and in Silico Admet Study of New 4-(Piperidin-1-Ylmethyl)-2- (Thiophen-2-Yl) Quinoline Analogues

Antiproliferative and in Silico Admet Study of New 4-(Piperidin-1-Ylmethyl)-2- (Thiophen-2-Yl) Quinoline Analogues

Antiproliferative, Adme and Potential in Silico G6pdh Inhibitory Activity of Novel 2-(1-Benzofuran-2-Yl)-4-(5-Phenyl-4h-1, 2, 4-Triazol-3-Yl) Quinoline Derivatives

Antiproliferative and Dna Cleavage Activity of Various Solvent Extracts of Acacia Farnesiana Linn. Pod

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