A new chalcone glycoside from Rhamnus nipalensis

Published in: Journal, Article, Volume : 22, Issue : 18, Pages : 1657-1659

DOI : 10.1080/14786410701876635

Author : Pandey, M. B.; Singh, A. K.; Singh, U.; Singh, S.; Pandey, V. B.

Abstract : A new chalcone glycoside, chalcone-2′,4-dihydroxy-4′-O-β-D-glucoside was isolated from Rhamnus nipalensis together with sitosterol, lupeol, di-O-methyldaidzein, kaempferol-4′-methylether, quercetin, physcion, sitosterol glucoside, emodin and their structures established by spectroscopic data. Isolation of these compounds are the first report from this plant.

Synthetic and spectroscopic studies of some new 2-[1-aryl-4{4-methoxyphenyl}-6-thioxo-1,6-dihydro-1,3,5-triazinyl]amino/ hydrazonothiazolidin-4-ones

Published in: Journal, Volume : 45, Issue : 3, Pages : 741-744

DOI : 10.1002/jhet.5570450317

Author : Roychowdhuary, P. K.; Upadhay, K. K.; Mishra, Rakesh K.; Kumar, Ajit; Mehrotra, Sangeeta; Srivastava, Sugandh; Upadhyay, Shalini

Abstract : A series of 4-thiazolidinones having triazinethione moieties have been synthesized by the systematic chem. modification of S-benzylmercapto-1-aryl-4-(4-methoxyphenyl)-1,6-dihydro-1,3,5-triazine-6-thione.

Cyclopeptide alkaloids from Zizyphus sativa bark

Published in: Journal, Article, Volume : 22, Issue : 3, Pages : 219-221

DOI : 10.1080/14786410601133483

Author : Pandey, Manoj Bhushan; Singh, Ashok Kumar; Singh, Virendra Pratap; Pandey, Vidya Bhushan

Abstract : A new cyclopeptide alkaloid, sativanine-M, together with known alkaloid nummularine-P were isolated from the stem bark of Zizyphus sativa and identified by spectral anal.

Exploring the potential of complex formation between a mutant DNA and the wild type protein counterpart: A MM and MD simulation approach

Published in: Journal, Article, Volume : 25, Issue : 1, Pages : 158-168

DOI : 10.1016/j.jmgm.2005.11.004

Author : Roy, Sujata; Sen, Srikanta

Abstract : We have demonstrated that the methods of mol. modeling and mol. dynamics simulation might be used to assess whether a specific mutation in the DNA would destabilize a known DNA-protein complex. The approach is based on probing the changes in the interaction that would be induced into the complex if within the already formed wild type complex the mutation could be introduced. We have used Hoxc8-DNA complex as a test system where it is known that the Hoxc8 binding affinity of the DNA is completely lost upon mutation of the DNA by replacing TAAT stretch to GCCG. Mutation was obtained by changing the relevant base pairs into the DNA of the model of the corresponding wild type complex developed by homol. modeling and MD simulation in water for 2.0 ns. Comparison of the structure, dynamics and interactions between the hypothetical mutant model with those of the similarly refined wild type model shows that the loss of affinity of the mutant DNA to Hoxc8 has two different origins: (i) loss of several strong H-bonds as the direct consequences of mutation and (ii) reduced H-bonds in the common parts due to a net loss or inferior H-bonding geometry induced by the mutation as indirect effects. The net change in the interaction energy between the DNA and the protein in the best possible configuration indicated the exptl. observed destabilization effects. No significant change in the groove width was observed and no correlation was found between the water-bridges and the loss of affinity.

Design and synthesis of potent non-peptidic inhibitors of HPTPβ

Published in: Journal, Article, Volume : 16, Issue : 16, Pages : 4252-4256

DOI : 10.1016/j.bmcl.2006.05.074

Author : Amarasinghe, Kande K. D.; Evidokimov, Artem G.; Xu, Kevin; Clark, Cynthia M.; Maier, Matthew B.; Srivastava, Anil; Colson, Anny-Odile; Gerwe, Gina S.; Stake, George E.; Howard, Brian W.; Pokross, Matthew E.; Gray, Jeffrey L.; Peters, Kevin G.

Abstract : The sulfamic acid phosphotyrosine mimetic was coupled with a previously known malonate template to obtain highly selective and potent inhibitors of HPTPβ. Potentially hydrolyzable malonate ester functionalities were replaced with 1,2,4-oxadiazoles without a significant effect on HPTPβ potency.

A Simple Approach for Indexing the Oral Druglikeness of a Compound: Discriminating Druglike Compounds from Nondruglike Ones

Published in: Journal, Article, Volume : 46, Issue : 3, Pages : 1394-1401

DOI : 10.1021/ci050459i

Author : Biswas, Dhrubajyoti; Roy, Sujata; Sen, Srikanta

Abstract : A knowledge-based simple score has been developed for indexing the oral druglikeness of compounds based on the concept that oral druglikeness should be independent of the drug targets and, thus, are closely related to the global absorption, distribution, metabolism, and excretion related properties. We have considered several simple mol. descriptors as the key determinants of druglikeness. The patterns of the distributions of these mol. descriptors for a set of drug mols. have been extracted using a nonlinear neural network method. We assumed direct correlations of these patterns to the expectation values that a given compound may behave like a drug. On the basis of this assumption, we have defined a simple druglike index or score (DLS) combining the contributions coming from the descriptors considered. This index scales the druglikeness of a compound in the range 0.0-1.0, 1.0 being the highest druglikeness. The index applied for a drug data set, a mixed data set, and three different bioactive databases produced expected features and indicated that even the marketed drugs have druglike scores varying over a considerable range. A total of 73.3% of the drugs considered showed DLS > 0.5, while it is only 44.7% for the HIC-Up compounds (unbiased ligand database). For the ChemBank, Asinex-Gold collection, and NCI databases 61.2%, 76.0%, and 79.1% of the compounds have DLS > 0.5.

One-pot synthesis of 1,2,4-oxadiazoles from carboxylic acid esters and amidoximes using potassium carbonate

Published in: Journal, Volume : 47, Issue : 22, Pages : 3629-3631

DOI : 10.1016/j.tetlet.2006.03.155

Author : Amarasinghe, Kande K. D.; Maier, Matthew B.; Srivastava, Anil; Gray, Jeffrey L.

Abstract : A convenient one-pot synthesis of 1,2,4-oxadiazoles is described. The condensation of carboxylic acid esters and amidoximes in the presence of potassium carbonate was employed to synthesize a variety of mono-, bis- and tris-oxadiazoles in moderate to excellent yields.

Homology modeling based solution structure of Hoxc8-DNA complex: Role of context bases outside TAAT stretch

Published in: Journal, Comparative Study, Article, Volume :22, Issue : 6, Pages : 707-718

DOI : 10.1080/07391102.2005.10507037

Author : Roy, Sujata; Sen, Srikanta

Abstract : The 3D structure of neither Hoxc8 nor Hoxc8-DNA complex is known. The repressor protein Hoxc8 binds to the TAAT stretch of the promoter of the osteopontin gene and modulates its expression. Over expression of the osteopontin gene is related to diseases like osteoporosis, multiple sclerosis, cancer et cetera. In this paper we have proposed a 3D structure of Hoxc8-DNA complex obtained by Homol. modeling and mol. dynamics (MD) simulation in explicit water. The crystal structure (9ant.pdb) of Antennapedia homeodomain in complex with its DNA sequence was chosen as the template based on (i) high sequence identity (85% for the protein and 60% for the DNA) and (ii) the presence of the TAAT stretch in interaction with the protein. The resulting model was refined by MD simulation for 2.0ns in explicit water. This refined model was then characterized in terms of the structural and the interactional features to improve our understanding of the mechanism of Hoxc8-DNA recognition. The interaction pattern shows that the residues Ile195, Gln198, and Asn199, and the bases S2-4TAATG8 are most important for recognition suggesting the stretch TAATG as the ‘true recognition element’ in the present case. A strong and long-lived water bridge connecting Gln198 and the base of S1-C7 complementary to S2-G8 was observed Our predicted model of Hoxc8-DNA complex provides us with features that are consistent with the available exptl. data on Hoxc8 and the general features of other homeodomain-DNA complexes. The predictions based on the model are also amenable to exptl. verification.

DNA topoisomerases in life and death: Implications in kinetoplastid protozoa

Published in: Journal, General Review, Article, Review Volume :4, Issue : 6, Pages : 711-722

DOI : 10.2174/1566524043360302

Author : Chowdhury, Arnab Roy; Majumder, Hemanta K.

Abstract : A review. Current biomedical research has its focus on the search for newer intervention strategies to control public health impact of parasitic diseases. The dramatic advances of mol. and cellular biol. in recent times have provided opportunities for discovering and evaluating mol. targets for drug designing, which now form a rational basis for the development of improved anti parasitic therapy. DNA topoisomerases, the “”cellular magicians”” involved in nearly all biol. processes governing DNA, have emerged as one such biol. target. Over the last 2 decades, interest in topoisomerases has expanded beyond the realm of the basic science laboratory into the clin. arena. This review aims at providing a comprehensive insight into the biol. of DNA topoisomerases and also focuses on its evolution as a drug target in the unicellular kinetoplastids.

2,4-Dinitroimidazole: Microwave assisted synthesis and use in synthesis of 2,3-dihydro-6-nitroimidazo[2,1-b]oxazole analogues with antimycobacterial activity

Published in: Journal, Volume :41, Issue : 1, Pages : 51-55

DOI : 10.1002/jhet.5570410108

Author : Bhaumik, Kankan; Akamanchi, K. G.

Abstract : 2,4-Dinitroimidazole (I), an important starting material for nitroimidazooxazole and nitroimidazooxazine types of antitubercular agents was synthesized by rearrangement of 1,4-dinitroimidazole under microwave irradiation Various new nitroimidazooxazoles analogs were prepared from I and were tested preliminarily against Mycobacterium tuberculosis, H37Rv strain. Some were found to be active.