Medicinal Chemistry

The hydrogen bond plays a vital role in structural arrangement, intermediate state stabilization, and biological activity of certain enzymatic reactions. The hybrid B3LYP functional was employed with 6-311++G(d, p) basis set for the exploration about the solvent effect on hydrogen-bonded acetic acid…arginine, acetic acid…imidazole, acetic acid…phenol dyads, as well as the Tyr…Asp…Arg triads. The difference of two hydrogen bonds lengths in every dyad is enlarged in diethyl ether solvent as compared to that in gas phase. The increasing of solvent dielectric constant enhances the isomers’ relative stability owing to the interaction between the polar conformer and the polarity solvent molecules. While the proton transfer barrier reduces. The linear relationship between dipole moment and stability can be utilized to estimate the stability modification by measuring the alteration of dipole moment of the dyad.

This review highlights the role of fluorescent dyes as active “molecular photoswiches” focusing on the application in bioimaging and anticancer therapies in the field of therapeutic delivery. The author describes the development of prodrugs targeted to specific cell types and polymeric nanocarriers (capsules, micelles and silica nanoparticles) used as fluorescent probes which offer advantages in the integration of “smart” features of fluorescent dyes into synthetic materials. The incorporation of biologically responsive components that cleave upon changes in pH or light irradiation is fundamental to the successful design of such carriers with capabilities to load and release therapeutics specifically at a target site.

A steady flow of reports suggests that proteasome inhibitor bortezomib promotes tumor cell death by degradation of key proteins. Therefore, bortezomib has been gaining intense attention as an anti-neoplastic agent, being the first proteasome inhibitor drug to be used in multiple myeloma´s treatment. However, new evidences point to the adverse effects of bortezomib leading to the poor outcome in both hematological and solid tumors. Despite its therapeutic effects, deciphering the molecular mechanisms of bortezomib action as well as the mechanism(s) of resistance to bortezomib in cancer remains a problem to be conquered.

Here, we report the synthesis of a series of dehydroabietylamine (DAA) salts. We studied the cytotoxic activity of DAA salts and their and antiviral properties against influenza virus A(H1N1)pdm09 We further compared these parameters to those of DAA itself and to organic acids used as counterions. We observed that the DAA, its hydrochloride (DAA∙HCl) and organic salts had similar cytotoxicity profiles in three cancer cell lines: MDA-MB-231, MCF-7, U-87 MG. Meanwhile the cytotoxicity of same organic salts of DAA with respect to melanoma cell line SK-Mel-8 was higher than those DAA and DAA∙HCl: CTD50 values of 5 from 14 synthesized salts were 2-2.8 times lower than that of CTD50 for DAA∙HCl. Pure organic acids used for the synthesis of DAA salts were noncytotoxic to cancer cells, except ursolic and glycyrrhetic acid having moderate cytotoxicity. Further, we found that modification of DAA with counterions derived from the selected organic acids does not affect, in most cases, the DAA antiviral activity (except compound 4n, DAA glycyrrhetate). The toxicity of this compound was significantly lower than that of its constituting ions, thereby making the selectivity index of this compound against the A(H1N1) pdm09 virus several times higher than that of other DAA salts.

A series of novel 5-[4-(substituted) benzylidine]thiazolidine-2,4-dione have been synthesized and evaluated for antidiabetic activity on male Wistar rats by Oral Glucose Tolerance Test (OGTT) method using pioglitazone as standard. The newly synthesized compounds have been characterized by IR, Mass and 1H NMR spectroscopic studies and report of them supports the structures of compounds. Comparison of data was performed by one way ANOVA followed by post-test, Dunnett’s multiple comparison tests. Some of the compounds have shown promising antidiabetic activity.

A new series of substituted quinolones linked to benzothiazole and/or benzoxazole moieties 5a-l was synthesized. 6-Benzoxazol-2-yl/benzothiazol-2-yl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl esters 3a&b were reacted with hydrazine to give the hydrazide derivatives 4a&b and finally, 4a&b were reacted with different aromatic aldehydes giving the target compounds 5a-l. The benzylidene derivatives 5a-l were screened for their cytotoxic activities against breast carcinoma cell lines (MCF-7) and anti-oxidant properties. All the tested compounds 5a-l showed from high to moderate activity as anticancer and anti-oxidant agents. Compounds 5h and 5l showed the highest cytotoxicr activity against MCF-7 (IC50: 0.058 and 0.052 uM, respectively) than 4-(benzothiazol-2-yl) aniline the reference drug (IC50: 0.065 uM). Moreover, compounds 5e, 5g and 5h showed the highest anti-oxidant activity. The structure of the compounds 5a-l was confirmed using IR, 1H NMR, mass spectroscopy and elemental analysis.

Galactomannans and xyloglucans can be isolated from seeds with relatively high purity and yield; they are water soluble, non-toxic, and biocompatible. These polymers have broad spectra of potential use in medicine, from drug delivery systems to biological response modifiers. The biological activity of polysaccharides is intrinsically linked to their structural aspects. In general the chemical modification of galactomannans and xyloglucans, e.g., sulfation and complexation with oxovanadium, potentiate effects such as cytotoxicity against tumor cells, leishmanicidal activity, and activation of macrophages to release proinflammatory mediators. The wide range of seeds and structural variety favor the isolation of galactomannans and xyloglucans. This allows derivatives to be obtained with targeted properties and activity enabling their use in new applications in the biomedical area.