Solvent-dependent activity of Candida antarctica lipase B and its correlation with a regioselective mono aza-Michael addition - experimental and molecular dynamics simulation studies.

With the aim of gaining understanding of the molecular basis of commercially available Candida antarctica lipase B (CALB) immobilized on polyacrylic resin catalyzed regioselective mono aza-Michael addition of Benzhydrazide to Diethyl maleate we decided to carry out molecular dynamics (MD) simulation studies in parallel with our experimental study. We found a correlation between the activity of CALB and the choice of solvent. Our study showed that solvent affects the performance of the enzyme due to the binding of solvent molecules to the enzyme active site region, and the solvation energy of substrates in the different solvents. We also found that CALB is only active in nonpolar solvent (i.e. Hexane), and therefore we investigated the influence of Hexane on the catalytic activity of CALB for the reaction. The results of this study and related experimental validation from our studies have been discussed here.

Synthesis and Cytotoxicity Study of New Cyclopenta [b] quinoline-1,8-dione Derivatives.

DNA intercalators belong to aromatic heterocyclic compounds interacting reversibly with DNA. These compounds have been used extremely as cytotoxic agents against cancer. In this study, the synthesis and biological activity of some novel derivatives of cyclopenta [b] quinoline-1, 8-dione as new intercalating agent were investigated. Twenty novel derivatives of cyclopenta [b] quinoline-1, 8-dione were synthesized by molecular condensation of equivalent amount of 3-imino cyclopentanone, corresponding aldehyde and cyclohexane-1, 3-dione. Then, their cytotoxic activity was evaluated against HeLa, LS180, MCF-7 and Raji cancer cell lines by MTT assay. The results of cytotoxic activity evaluation indicate that the most of synthesized compounds show weak cytotoxic effect on the different cell lines (IC50 of these compounds is higher than 50 or 100 µ ). According to previous studies, in the case of compounds with the weak biological activity, it is more suitable to use IC15 and IC30 instead of IC50 as the indicator of biological activity. Since most of compounds have weak cytotoxic effect, we also calculated IC15 and IC30 for evaluating the cytotoxic activity of synthesized compounds. The most potent compound, 6 h (9-(3-Bromo-phenyl)-4-pheny l-2, 3, 5, 6, 7, 9-hexahydro-4H-cyclopenta [b] quinoline-1, 8-dione), containing bromophenyl moiety and phenyl substitute on nitrogen of central quinoline ring, show significant cytotoxic activity especially in Raji and HeLa cell lines (IC30: 82 and 24.4 µ M respectively) comparing to other compounds. Although the results of cytotoxic activity evaluation demonstrated that the in-vitro anti-cancer effect of synthesized compounds are mainly low, it seems that this structure can be used as a novel cytotoxic scaffold for further modification and design of novel potent compounds.

Chromene-based synthetic chalcones as potent antileishmanial agents: synthesis and biological activity.

Two types of regioisomeric chromene-based chalcones namely, 1-(6-methoxy-2H-chromen-3-yl)-3-phenylpropen-1-ones and 3-(6-methoxy-2H-chromen-3-yl)-1-phenylpropen-1-ones were prepared and investigated for their antileishmanial activity against promastigotes form of Leishmania major. The obtained results from in vitro biological assays indicated that chloro-substituted 1-(6-methoxy-2H-chromen-3-yl)-3-phenylpropen-1-ones exhibited excellent activity against Leishmania major at non-cytotoxic concentrations.

Novel antileishmanial chalconoids: synthesis and biological activity of 1- or 3-(6-chloro-2H-chromen-3-yl)propen-1-ones.

A series of novel chalconoids containing a 6-chloro-2H-chromen-3-yl group were prepared through a convenient and efficient synthetic method by using 5-chloro-2-hydroxybenzaldehyde as starting material. The target compounds were evaluated against the promastigote form of Leishmania major using MTT assay. All of the evaluated compounds have shown high in vitro antileishmanial activity at concentrations less than 3.0 microM. The results of cytotoxicity assessment against mouse peritoneal macrophage cells showed that these compounds display antileishmanial activity at non-cytotoxic concentrations.