Medicinal Chemistry

The MMP-13 inhibition activity of non-zinc-chelating compounds has been quantitatively analyzed in terms of chemometric descriptors. The statistically validated quantitative structure-activity relationship (QSAR) models provided rationales to explain the inhibition activity of these compounds. The descriptors, identified through combinatorial protocol in multiple linear regression (CP-MLR) analysis, have highlighted the role of 3-path Kier alpha-modified shape index (S3K), complementary information content index of 1-order neighborhood symmetry (CIC1), eigenvalue sum from mass weighted distance matrix (SEigm), lowest eigenvalue n. 6 of Burden matrix / weighted by atomic van der Waals volumes (BELv6) and by atomic polarizabilities (BELp6), 3-order topological charge index (GGI3) and the functionality, R--CR--R (C-025). From statistically validated models, it appeared that the descriptors S3K, BELv6, BELp6 and SEigm make positive contribution to activity and their higher values are conducive in improving the MMP- 13 inhibition activity of a compound. On the other hand, the descriptors CIC1, GGI3 and C-025 render detrimental effects to activity. Therefore, the absence of functionality, R--CR--R and lower values of descriptors CIC1 and GGI3 would be advantageous. PLS analysis has further corroborated the dominance of the CP-MLR identified descriptors. Applicability domain analysis revealed that the suggested models have acceptable predictability. All the compounds are within the applicability domain of the proposed models and were evaluated correctly.

The ErbBreceptor family has been used as therapeutic target for treatment of several types of cancer. Biflorin is a natural ο-naphthoquinone with anticancer properties. Herein, we described the effect of biflorin on cell growth and EGFR expression in SK-Br3 human breast cancer cell line with high EGFR expression. Biflorin significantly inhibited breast cancer cell growth, in a dose- and time-dependent manner as determined by the Alamar Blue assay. Noncitotoxicity were observed in normal MCF-10A breast cell line. Furthermore, biflorin inhibited EGFR expression in a dose-dependent manner. Biflorin can be used as a drug lead for new molecules against EGFR.

Rapid, sensitive, simple and accurate high-performance liquid chromatographic (HPLC) method is developed and validated for the simultaneous determination of captopril with H2 receptor antagonists as cimetidine, ranitidine and famotidine. Captopril was separated from H2 receptor antagonist using pre packed Purospher star C18 (5 μm, 25×0.46 cm) column methanol: water (60:40 v/v) were used as the mobile phase, pH 3.0 ± 0.02 was adjusted by orthophosphoric acid. The flow rate was 0.8 mLmin-1 at ambient temperature, diluent was 50:50 methanol water while UV detection was performed at 225 nm. The retention time for captopril was found to be 5.2 minute, for ranitidine and famotidine 2.5 minute and cimetidine 2.7 minute. Each drug showed a good resolution from captopril. In vitro interaction studies of captopril with commonly administered H2 receptor antagonists i.e. cimetidine, ranitidine and famotidine were carried out at 37°C using above validated method. These studies clearly indicated that H2-receptor antagonists bind to captopril causing drastic changes in the availability of the drug.

We report herein the synthesis of series of 9-substituted derivatives of tert-butyl 6-(9H-purin-6-ylthio) hexylcarbamate by the reaction of tert-butyl 6-(9H-purin-6-ylthio) hexylcarbamate with different acid chlorides using triethylamine in Dichloromethane solvent.