Maddamsetty V. Rao

Recent Developments in the Design, Synthesis and Structure-Activity Relationship Studies of Pyrrolo[2,1-c][1,4]benzodiazepines as DNA-Interactive Antitumour Antibiotics

Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are naturally occurring compounds isolated from various Streptomyces species. The PBDs exert their biological activity through covalent binding and exhibit cytotoxicity. Extensive studies have been carried out on the synthetic strategies of PBDs, and a sound understanding of structure activity relationships within this class of compounds has been developed. The PBDs have shown to interfere with the interaction of endonuclease enzymes of DNA and block the transcription by inhibiting RNA polymerase in a sequence specific manner. These processes have been thought to account for the biological activity of PBDs. The PBDs have also been used as a scaffold to attach different type of moieties leading to novel sequence selective DNA cleaving and cross-linking agents. The design and synthesis of C8-linked PBD dimers and other hybrids of PBDs has given a new insight towards the development of molecules with enhanced DNA binding affinity and sequence specificity compared to the naturally occurring PBDs. This improvement in the biological profile has been explained on the basis of certain factors like DNA cross-linking and doubling of DNA binding sites. There seems to be enough potential for further changing the substitution pattern and to design structurally modified PBDs by retaining the PBD core intact. In this review both the synthetic strategies and the structure-activity relationships, particularly the DNA binding and cytotoxicity studies of PBDs have been discussed.

Recent Advances in the Solid-Phase Combinatorial Synthetic Strategies for the Quinoxaline, Quinazoline and Benzimidazole Based Privileged Structures

Quinoxaline, quinazoline and benzimidazole based templates have been synthesized on solid-support employing different methodologies. This review enlightens academic and industrial examples of combinatorial synthesis for this type of heterocycles that appeared in the literature in the last decade. Hence, some of the important synthetic strategies for the generation of quinoxaline, quinazoline and benzimidazole based privileged structures, and the important biological activities for these heterocycles have been highlighted. Further, benzothiadiazinone, thioxoquinazolinone, cinnoline and indazole are also examined in this review.

Enantioselective ring opening of epoxides with trimethylsilyl azide (TMSN3) in the presence of β-cyclodextrin: an efficient route to 1,2-azido alcohols

Abstract The ring opening of epoxides with nucleophiles such as TMSN 3 and isopropylamine takes place enantioselectively in the presence of β-cyclodextrin under extremely mild conditions and the azido alcohols and amino alcohols are formed as ( S )-isomers.

Stereoselective synthesis of (S)-propanol amines: Lipase catalyzed opening of epoxides with 2-propylamine

Abstract The ring opening of epoxides with 2-propylamine in presence of lipase in organic solvents affords selectively (S)-propanol amines. The effect of solvents towards selectivity has also been examined.

Efforts Towards the Development of New Antitubercular Agents: Potential for Thiolactomycin Based Compounds

Development of new chemotherapeutic drugs is the need of the hour to improve tuberculosis control, particularly in the developing world. In the last fourty years no new compound has been brought to the market for the treatment of tuberculosis. However, in recent years there is an enhanced activity in the research and development of new drugs for TB. Some compounds are presently in clinical development, while others are being investigated pre-clinically in an attempt to explore new molecules for the target based treatment of TB. Simultaneously some new targets are being identified and validated for their practical usefulness. Structures based on thiolactomycin could have considerable potential in the development of target based anti-TB agents. The present review provides an overview of the drugs that are being clinically used and the compounds that are in advanced stages of clinical as well as preclinical studies. We have also attempted to highlight the efforts that are being made in the development of new molecules based on thiolactomycin as lead compound, including studies from this laboratory.

Stereoselective synthesis of (S)-propanol amines: Liver microsomes mediated opening of epoxides with arylamines

Abstract Stereoselective synthesis of 2-(S)-propanol amines by the ring-opening of racemic epoxides with arylamines in presence of rat liver microsomes.

Efficient enzymatic hydrazone hydrolysis by baker's yeast

Abstract The quantitative enzymatic conversion of N -phenyl and N,N -dimethyl hydrazones by bakers yeast to the corresponding aldehydes and ketones is described.

Enzyme catalyzed stereoselective synthesis of (S)-propanolamines

Abstract Stereoselective synthesis of (S)-propanolamines has been carried out by the ring opening of racemic epoxides with 2-propylamine in presence of lipases and subtilisin. The effect of solvent towards selectivity has also been studied.

Lipase-catalyzed resolution: Enantioselective esterification of 2-propanol amines

Abstract Porcine pancreatic lipase catalyzes the specific hydroxyl acylation of 2-propanol amines with enantioselectivity employing trichloroacetic anhydride in organic solvents.

Efficient Enzymatic Cyclization of 2-(Carbamoyloxy)- and 2-(Sulfamoyloxy)benzonitriles by Ultrasonically Stimulated Baker's Yeast

An approach to the synthesis of 4-imino substituted 1,3-benzoxazin-2-ones, 1,2,3-benzoxathiazin-2-ones and 2-quinazolinones based on the enzymatic cyclisation of the labile-functionalized compounds with ultrasonically bakers yeast.