Armaceutical Sciences 2013, 21:31 http://www.darujps/content/21/1/Page 7 ofTable 1 Cytotoxic activity (IC50, g/ml) of compounds 5a-k against different cell lines in comparison with etoposideO Ar MeOCompounds 5aHO MeOOMDA-MB-231 KB 36.85 two.97 SK-N-MC 12.60 8.ArCl19.70 3.5bMeOCl7.56 two.25.04 ten.9.64 2.MeO5cO MeO OCl20.03 four.58.04 21.MeO5dO MeO OClEtOCl5eO EtO OEtO5fO MeO O16.47 1.5gO EtO O16.32 two.5hO n-PrO O18.87 0.5iO n-BuO O7.10 2.Noushini et al. DARU Journal of Pharmaceutical Sciences 2013, 21:31 http://www.darujps/content/21/1/Page eight ofTable 1 Cytotoxic activity (IC50, g/ml) of compounds 5a-k against distinct cell lines in comparison with etoposide (Continued)5jO MeO O14.23 4.5kO MeO O10.53 0.Etoposide21.two two.18.93 1.14.04 1.8a-c. On the other hand, O-methylation of compound 7a afforded dimethoxybenzaldehyde derivative 9a. Methyl (formylphenoxy)acetate 11a-c was synthesized by heating compounds 10a-c with methyl bromoacetate and potassium carbonate in ethyl methyl ketone.In vitro cytotoxic activityThe cytotoxic activity of synthesized compounds 5a-k was evaluated against 3 cell lines namely MDA-MB231 (breast cancer), KB (nasopharyngeal epidermoid carcinoma) and SK-N-MC (human neuroblastoma) cells. The outcomes of cytotoxic assay have been pointed out as IC50 (g/ml) of compounds in comparison with reference drug etoposide in Table 1. In the case of MDA-MB-231 cell line, the IC50 values of all compounds have been 20 g/ml with the exception of compounds 5d and 5e. Additionally, compounds 5b and 5i exhibited the highest cytotoxic activity against this cell line (IC50 ten g/ml). Compound 5b was also probably the most potent derivative against KB cell line with IC50 worth of 25.04 g/ml. Beside compound 5b, compound 5a exhibited superior activity against KB cells, but remaining compounds 5c-k showed no activity against this cell line (IC50 100 g/ml).Flucytosine Against SK-N-MC cells, compound 5b followed by compounds 5a and 5c showed substantial inhibitory activity with IC50 values of 9.64, 12.6 and 58.04 g/ml, respectively. All round, it is clear that amongst the test compounds described within this study, the 3-chloro-4,5-dimethoxybenzylidene derivative 5b demonstrated improved cytotoxic profile against all tested cell lines (IC50 values = 7.Brazikumab 5625.PMID:23910527 04 g/ml). Usually, the comparison of IC50 values of compound 5b with those of etoposide demonstrated that the cytotoxic activity of compound 5b against MDAMB-231 and SK-N-MC cells is more than etoposide. In this operate, as a part of an ongoing program to discover new cytotoxic agents, we’ve got focused our attention on modification on the 3-benzylidene-4-chromanones and introducing new functionality around the benzylidene moiety.Therefore, we created novel 3-benzylidene-4-chromanones that possessed a 2-(2-chloro-6-alkoxyphenoxy)acetic acid ester. These modifications have been created on the basis of SJ172550, a new cytotoxic agent possessing 2-(2-chloro-6ethoxyphenoxy)acetic acid methyl ester attached for the pyrazolone ring. Surprisingly, compound 5d, the chromanone analog of SJ-172550 showed no activity against tested cell lines. Also, the ethyl ester counterpart of 5d (compound 5e) was inactive against tumor cell lines. Even so, the 2-(2-chloro-6-methoxyphenoxy)acetic acid methyl ester analog 5c was active against MDA-MB-231 and SK-N-MC cells. We have briefly investigated the SAR of compounds by simplification of your functionality around the benzylidene part of the fundamental molecule. As is usually deduced from the cytotoxic data of compounds 5f-k which characterized by the l.