Anti-Infective Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Infective Agents) - Volume 9, Issue 2, 2010

Background: We have recently reported that Lactobacillus GG (LGG) elaborates seven small peptides that exert both anti- Gram-negative and Gram-positive bactericidal activity. Among them, peptides NPSRQERR, VHTAPK and PDENK have higher activity than others. Here we further report the inhibitory function of these three peptides on antibiotic- resistant bacterial strains and preliminary structure-activity analysis. Methods: Peptides were synthesized, purified, and dissolved in related media. Lactobacillus GG conditioned medium was used as a positive control and media alone or homologous-conditioned medium were used as negative controls. A600 measurement was used to measure antibacterial activity. Results: LGG-derived peptides NPSRQERR, VHTAPK and PDENK were found to inhibit growth of kanamycin-resistant E. coli SM10 δpir and tetracycline-resistant E. coli TOPO10. Moreover, growth of methicillin-resistant Staphylococcus aureus (MRSA) was also found to be inhibited by peptides NPSEQERR, VHTAPK and PDENK. Structurefunction analyses revealed that the anti-bacterial properties of these peptides can be increased or decreased by modification of amino acid charge.

The work describes QSAR and SAR studies on the TIBO derivatives as non-nucleotide reverse transcriptase inhibitor of HIV-1 using the 2D-topological, physicochemical and hydrophobic parameters, indicator parameters along with the some 3D or quantum parameters. The set of TIBO derivatives chosen for the modeling is consists of 20 compounds. Application of multiple linear regression analysis indicated that a combination of adhoc molecular descriptors and the indicator parameters yielded a statistically significant model for the prediction of activity, log1/C (50% of Effective concentration for inhibition of reverse transcriptase-1 of HIV.). The final selection of a potential TIBO derivative as non-nucleotide reverse transcriptase inhibitor of HIV-1 is made by the quantum molecular modeling.

Tuberculosis (TB) has remained an enemy of humankind before the beginning of recorded history. Although it is curable and preventable, TB claims the lives of more than 5,000 people every day. Despite of availability of effective chemotherapy and BCG vaccine in 21st century, TB remains one of the most deadly infectious diseases. The concomitant resurgence of TB with the Multi-drug resistant (MDR) or Extremely drug resistant (XDR)-TB and HIV/AIDS pandemic raises the threat posed by untreatable and fatal human TB, exposing the frailties of the current drug armatorium. No new drug is available acting through novel mechanism since last 40 years. The genome of Mycobacterium tuberculosis H37Rv was sequenced in 1998 and reannotated in 2002. This coupled with development of new genetic tools, have greatly contributed to the discovery of potential drug targets for new anti-TB agent. It is increasingly acknowledged that new drugs should not only be active against drug resistant TB, but should also kill persisters and shorten the lengthy TB treatment, which underlies the problem of drug resistance due to poor compliance to the length of therapy. This review article describes the current TB drugs, their merits and demerits as well as the new promising anti-TB agents classified on the basis of molecular framework. It is a comprehensive literature compilation on the present research paradigm of anti-TB drug discovery including advances in the new structural analogs reported in last decade.