Amino acid chirons: a tool for asymmetric synthesis of heterocycles.

As a result of their easy availability in enantiomerically enriched form and their possession of synthetically transformable diverse functional groups, amino acids have been extensively used by synthetic organic and medicinal chemists as a chiral pool for access to heterocycles (monocycles, bicycles or polycycles, either bridged or fused). This review describes the syntheses of diverse asymmetric heterocycles with various membered rings (n = 3-9) followed by benzo or heteroannulated ones, for the period from 1996 to Dec. 2013. It details solution phase synthetic methodologies in which the naturally occurring α-amino acid is incorporated, totally or partially, into the final product.

Arsenic induced myocardial toxicity in rats: alleviative effect of Trichosanthes dioica fruit.

The present study investigated the alleviative effect of aqueous extract of Trichosanthes dioica fruit (AQTD) against arsenic induced cardiotoxicity in Wistar albino rats. AQTD (50 and 100 mg/kg) was administered orally to rats for 20 consecutive days before oral administration of sodium arsenite (10 mg/kg) for 8 days. Then the body weights, heart weights, hematological profile, serum biochemical profile; myocardial antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and DNA fragmentation were evaluated. Pretreatment with AQTD markedly and significantly normalized body weights, heart weights, hematological profile, serum biochemical profile and significantly modulated all the myocardial antioxidative parameters and reduced DNA fragmentation in arsenic intoxicated rats. Therefore, T. dioica fruit possessed remarkable alleviative effects against arsenic induced myocardial toxicity in Wistar albino rats mediated by amelioration of arsenic induced myocardial oxidative stress by several mechanisms.

Rationalized design, synthesis and pharmacological screening of amino acid linked spiro pyrrolidino oxyindole analogs through environment friendly reaction.

INTRODUCTION: The development of newer synthetic approaches toward the synthesis of polynuclear heteroaromatics and their application in the synthesis of some biologically active compounds has been discussed in this study. MATERIALS AND METHODS: The synthesis of novel spiro pyrrolidino oxindoles was performed for the construction of amino acid linked polynuclear heteroaromatics by cycloaddition reaction. This reaction method is one of the most important methods for the construction of spiro pyrrolidino oxindole from the commercially available starting material isatin. Then the synthesized compounds were subjected for evaluation of nitric oxide scavenging and cytotoxic effects against tumor cell lines. RESULTS: All the six synthesized compounds demonstrated promising antioxidant and cytotoxic effects in vitro. CONCLUSION: Form the present study, it can be concluded that the synthesized compounds are fruitful in terms of their chemical purity, structural novelty, marked biological activities (antioxidant and cytotoxic) in vitro and last of all the lucid and picturesque synthetic methodology to synthesize the molecules in a in a non-hazardous and environmental friendly way.

Aryl aryl methyl thio arenes prevent multidrug-resistant malaria in mouse by promoting oxidative stress in parasites.

We have synthesized a new series of aryl aryl methyl thio arenes (AAMTAs) and evaluated antimalarial activity in vitro and in vivo against drug-resistant malaria. These compounds interact with free heme, inhibit hemozoin formation, and prevent Plasmodium falciparum growth in vitro in a concentration-dependent manner. These compounds concentration dependently promote oxidative stress in Plasmodium falciparum as evident from the generation of intraparasitic oxidants, protein carbonyls, and lipid peroxidation products. Furthermore, AAMTAs deplete intraparasite GSH levels, which is essential for antioxidant defense and survival during intraerythrocytic stages. These compounds displayed potent antimalarial activity not only in vitro but also in vivo against multidrug-resistant Plasmodium yoelii dose dependently in a mouse model. The mixtures of enantiomers of AAMTAs containing 3-pyridyl rings were found to be more efficient in providing antimalarial activity. Efforts have been made to synthesize achiral AAMTAs 17-23 and among them, compound 18 showed significant antimalarial activity in vivo.

Deciphering the Structural Requirements of Nucleoside Bisubstrate Analogues for Inhibition of MbtA in Mycobacterium tuberculosis: A FB-QSAR Study and Combinatorial Library Generation for Identifying Potential Hits.

The re-emergence of tuberculosis infections, which are resistant to conventional drug therapy, has steadily risen in the last decade. Inhibitors of aryl acid adenylating enzyme known as MbtA, involved in siderophore biosynthesis in Mycobacterium tuberculosis, are being explored as potential antitubercular agents. The ability to identify fragments that interact with a biological target is a key step in fragment based drug design (FBDD). To expand the boundaries of quantitative structure activity relationship (QSAR) paradigm, we have proposed a Fragment Based QSAR methodology, referred here in as FB-QSAR, for deciphering the structural requirements of a series of nucleoside bisubstrate analogs for inhibition of MbtA, a key enzyme involved in siderophore biosynthetic pathway. For the development of FB-QSAR models, statistical techniques such as stepwise multiple linear regression (SMLR), genetic function approximation (GFA) and GFAspline were used. The predictive ability of the generated models was validated using different statistical metrics, and similarity-based coverage estimation was carried out to define applicability boundaries. To aid the creation of novel antituberculosis compounds, a bioisosteric database was enumerated using the combichem approach endorsed mining in a lead-like chemical space. The generated library was screened using an integrated in-silico approach and potential hits identified.