Letters in Drug Design & Discovery - Volume 4, Issue 8, 2007

In order to develop novel therapies for the treatment of central nervous system diseases, methods for rapid quantification of different neural cell populations, from healthy or diseased brains, are highly desirable. Today, the method of choice to quantify different cell populations in the brain is immunohistochemistry. This technique is precise and reliable, but is also very time consuming and cost-intensive. In this paper, we descr Read More

We evaluated whether V-5 Immunitor (V5), tableted immunotherapeutic preparation comprising heatinactivated HBV antigens from pooled blood of HBV- and HCV-infected donors, may produce clinical benefit through induction of oral tolerance and reduction of immune-mediated liver injury. Once daily dose of V5 was administered per os to 10 patients with chronic hepatitis B in an open label study that lasted one month. Ever Read More

We report the results of the evaluation of a series of benzyl imidazole-based compounds against the enzyme aromatase (AR). The results show that the synthesised compounds were potent inhibitors of AR in comparison to the standard compound aminoglutethimide (AG).

A new series of benzothiazolo-benzothiadiazine hybrids (9a-g) has been synthesized and evaluated for their antibacterial activity against clinical isolates of Gram-positive and Gram-negative bacteria. Some of these hybrids in this series exhibited antibacterial activity comparable to ampicillin. In addition, some of the compounds showed DNA gyrase inhibitory activity at a moderate level compared to ciprofloxacin.

Mitogen-activated protein kinase-activated protein kinase 2 (MK-2) plays an important role in treatment of inflammatory disease such as rheumatoid arthritis. CoMFA was conducted on thirty-one analogs displaying variable inhibition of MK-2 to determine the structural requirements for potency in inhibiting MK-2. The resulting model exhibited good q2 and r2 values up to 0.549 and 0.973 for CoMFA, the standard error of Read More

Two microplate assays for inhibitor testing were established and used to identify new hyaluronidase inhibitors from a series of benzimidazole derivatives. In vitro assays were performed at pH 7 using a “stains-all” based assay and at pH 3.5 using a Morgan-Elson assay. Twelve benzimidazole derivatives were synthesized and tested on hyaluronidase inhibition at a concentration of 100 μM and IC50 values of the c Read More

The cysteine hydrolase N ω,N ω-dimethyl-L-arginine dimethylaminohydrolase-1 (DDAH-1) is an important regulator of NO production through the degradation of endogenous Nω-methylated arginines, that are competitive inhibitors for nitric oxide synthase (NOS). Consequently, DDAH-1 is a target for pharmacological drug design to regulate NO production. The appearance of a second isoform DDAH-2, which was assigned th Read More

A new method for the synthesis of quinolines has been developed by employing various novel catalysts such as Al(OTf)3, Gd(OTf)3, and TMSCl-NaI. Later, these compounds were condensed with 3-hydrazino benzothiadiazines to obtain quinoline derived [1,2,4]triazolo[1,5-b][1,2,4] benzothiadiazines. Further, these new molecules have been evaluated for their antibacterial activity and some of them have exhibited si Read More

Molecular orbital calculations are used to determine structural and electronic characteristics of a series of sugar mimics, which are correlated with experimentally determined activity toward glycosidases. Differences in activity between α- and β-glycosidase correlate to the position of the HOMO surface of the neutral form of the inhibitor. A correlation is also found between relative activity and energy of the HOMO.

New A-C8 and C-C2-linked 6-chloropurine-pyrrolo[2,1-c][1,4]benzodiazepine hybrids have been prepared and evaluated for their anticancer potential. The molecular modeling studies might be explained in terms of effect of the molecule on binding in the minor groove of DNA and also comparison to both A-C8/C-C2-position of the PBD. These PBD conjugates have shown DNA-binding ability and promising anticancer activity.

To discover new potential sigma ligands, a library of 64 members based on a carbamidic scaffold was designed and a synthetic protocol, based on PASPS and MAOS techniques, was developed and optimized. Applying the developed protocol the library compounds were obtained in high purity, suitable for biological screening.