L-谷氨酸类似物作为潜在抗癌剂的合成与评价

Synthesis and evaluation of L-glutamic Acid analogs as potential anticancer agents.

作者信息

Vishwanathan C L, Deb S, Jain A, Lokhande T, Juvekar Aarti

机构信息

Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai-400 098, India.

出版信息

Indian J Pharm Sci. 2008 Mar-Apr;70(2):245-9. doi: 10.4103/0250-474X.41467.

DOI:10.4103/0250-474X.41467

PMID:20046724

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2792474/

Abstract

Four N-(benzenesulfonyl)-L-glutamic acid bis(p-substituted phenylhydrazides) were synthesized and evaluated for anticancer activity in vitro in DU-145 and PC-3 prostate cancer and in COLO-205 colon cancer cell lines by MTT assay. The analog with the nitro group substitution exhibited potent activity (% Inhibition 84.7 and 72.0 in DU-145 and PC-3 respectively at 80 mug/ml concentration). Another series of substituted 1-(benzenesulfonyl)-5-oxopyrrolidine 2-carboxamides (11a-f) were synthesized and evaluated for anticancer activity in vitro in colon (COLO-205), breast (Zr-75-1) and prostate (PC-3) cancer cell lines by MTT assay using adriamycin as standard. Test compounds 11a-c showed potent activity (% Inhibition 61.2 to 79.2 at 20 mug/ml and 67.2 to 87.2 at 40 mug/ml) in PC-3 cell line which is superior to the activity of Adriamycin. In comparison compounds 11d-f were less potent. In Zr-75-1 cell line 11a-e showed % inhibition ranging from 32.4 to 54.9 at 10 mug/ml concentration while in COLO-205 cell line 11a-f showed poor activity.

摘要

合成了四种N-(苯磺酰基)-L-谷氨酸双(对取代苯肼)，并通过MTT法在DU-145和PC-3前列腺癌细胞系以及COLO-205结肠癌细胞系中对其体外抗癌活性进行了评估。硝基取代的类似物表现出较强的活性(在80μg/ml浓度下，DU-145和PC-3中的抑制率分别为84.7%和72.0%)。合成了另一系列取代的1-(苯磺酰基)-5-氧代吡咯烷-2-甲酰胺(11a-f)，并以阿霉素为标准，通过MTT法在结肠(COLO-205)、乳腺(Zr-75-1)和前列腺(PC-3)癌细胞系中对其体外抗癌活性进行了评估。测试化合物11a-c在PC-3细胞系中表现出较强的活性(在20μg/ml时抑制率为61.2%至79.2%，在40μg/ml时抑制率为67.2%至87.2%)，优于阿霉素的活性。相比之下，化合物11d-f的活性较弱。在Zr-75-1细胞系中，11a-e在10μg/ml浓度下的抑制率为32.4%至54.9%，而在COLO-205细胞系中，11a-f的活性较差。