Nitric Oxide Releasing Derivatives of [(2-Chloroethyl)ureido] Benzoic Acid Esters as Potential Antineoplastic Agents

• Published in: Turkish journal of chemistry Vol. 33; no. 1; pp. 107 - 121
• Main Authors: AKGÜN, HÜLYA, BERK, BARKIN, EROL, DİLEK DEMİR, MERCANOĞLU, GÜLDEM, BAYRAK, ÖMER FARUK, ÇAĞLAYAN, BERRAK, DEDEAĞAÇ, ASLI, KURNAZ, IŞIL AKSAN
• Format: Journal Article
• Language: English
• Published: TÜBİTAK 01-01-2009
• ISSN: 1303-6130; 1300-0527; 1303-6130
• DOI: 10.3906/kim-0807-25

New series of [(2-chloroethyl)ureido] benzoic acids (compounds 3-8) and nitric oxide releasing derivatives
of [(2-chloroethyl)ureido] benzoic acid esters (compounds 9-14) were synthesized as potential anti-cancer
agents. These compounds were screened for their anti-proliferative activities on A549 (human lung carcinoma)
cells and for their cytotoxic effects on L929 (mouse fibroblast) cells. The compounds 3-8 exhibited mild
cytotoxic effects on L929 cells (cell viability from 100% to 85% - 90% only) whereas they had very little antiproliferative
activities towards A549 lung carcinoma cells. On the other hand, compounds 10, 11, and 13 had
some growth inhibition activity in A549 (human lung carcinoma) cells. Among them, compounds 11 and 13
exhibited better anti-proliferative activities towards A549 cells, but also appeared to be cytotoxic towards
L929 cells. In this group, the compound 10 with (1-(2-nitrooxyethyl)-3-[(2-chloroethyl)ureido]benzoate)
structure appeared to have very weak anti-neoplastic activity towards A549 cells, with very little cytotoxic
activity towards fibroblasts at physiological concentrations. Therefore, this compound is a better candidate
for a potential anti-cancer therapy for non-small cell lung carcinomas. However, further studies are required
in order to show applicability and effectiveness in animal models for this type of cancer.