Ack of 2chloro-6-alkoxy functionality, the cytotoxic activity against MDA-MB-231 is often served by the simple phenoxyacetic acid ester derivatives. Even so, the lack of 2-chloro-6-alkoxy functionality leads to the lack of activity against KB and SK-N-MC cells. Among the compounds 5f-k, butyl ester derivative 5i showed the highest activity against MDA-MB-231 getting 3-fold more potent than typical drug etoposide. To figure out the impact of acetic acid ester substitution in compound 5c, we ready both the 4-hydroxy derivative 5a and 4-methoxy analog 5b. When when compared with 5c, both compounds had comparable or better in vitro activities against tested cell lines. The cytotoxic activities of regio-isomeric compounds 5f, 5j and 5 k against MDA-MB-231cells revealed that altering the position of oxyesteric group has led to non-significant modifications in activities.Acetylcysteine As seen from data, in poly-substituted compounds altering of methoxy group on phenyl ring to ethoxy group (as an example 5d versus 5c) dramatically decreased the cytotoxic potency in MDA-MB-231 and SK-N-MC cells. In summary, in the pursuit for discovering new cytotoxic agents, we replaced the pyrazolone element of well-knownNoushini et al. DARU Journal of Pharmaceutical Sciences 2013, 21:31 http://www.darujps/content/21/1/Page 9 ofcytotoxic agent SJ-172550 with 7-methoxychroman-4one. Despite the fact that the direct analog of SJ-172550 (compound 5d) didn’t show any cytotoxic activity against tested cell lines, but 2-(2-chloro-6-methoxyphenoxy) acetic acid methyl ester analog 5c showed some activity against MDA-MB-231 and SK-N-MC cells. Additional modification of compound 5c resulted in the 3-chloro-4,5dimethoxybenzylidene derivative 5b which demonstrated far better cytotoxic profile against all tested cell lines (IC50 values = 7.565.04 g/ml). It can be worthwhile to mention that, because we’ve originally made the target compounds based on p53dependent cytotoxic agent SJ-172550, it was superior using the latter compound as common drug in our cytotoxic assay. However, our primary cytotoxic experiments on the closest compound to SJ-172550 (compound 5d) within a side-by-side comparison manner with etoposide revealed that compound 5d had no activity against cancer cell lines. On the other hand, simplified compounds 5a and 5b with a lot more dissimilarity respect towards the SJ-172550 showed improved profile of cytotoxicity. Primarily based on these benefits, it appears that a various mechanism is responsible for potential cytotoxic activity of compound 5b prototype. We employed MTT cell viability assay as a typical and well-documented in vitro technique for evaluation of the cytotoxic prospective of made compounds.Atazanavir sulfate Even though these kinds of in vitro models are valuable and promising as early screening tools for obtaining new lead compounds, but these models are related with some limitations [23].PMID:23600560 As a result, for efficacy and security evaluation of lead compounds, conducting a process based on animal model is vital within the subsequent steps of study. In conclusion, the results demonstrated that the cytotoxic activity of 3-(3-chloro-4,5-dimethoxybenzylidene)7-methoxychroman-4-one (5b) against MDA-MB-231 and SK-N-MC cells is more than typical drug etoposide. Hence, compound 5b prototype bearing 3-chloro-4,5dimethoxybenzylidene moiety might be regarded as as novel lead compound for further building new anticancer chemotherapeutics. Though, compound 5b showed promising activity in vitro, but to determine a promising anticancer drug candidate that has superior phar.
