Anindra Sharma

Carbohydrate based Potential Chemotherapeutic Agents: Recent Developments and their Scope in Future Drug Discovery

In addition to being valuable source of energy, carbohydrates, one of the main dietary components, are integral parts of the cell. As extra- & intracellular molecules they act as cell surface receptor and also as signaling molecules playing predominant role in molecular recognition and many other cellular processes. The clear understanding of their role in the various important biological events has led to the demand for easy access of diverse glycoconjugates for their complete chemical and biological investigations. Several carbohydrate-based molecules both of synthetic and natural origin are known for their wide range of pharmacological activities and even many of them are clinically used to treat different ailments. Due to their structural diversity in terms of functional groups, ring size and linkages they are valuable scaffolds in drug discovery processes. Because of the hydrophilic nature of monosaccharides they offer good water solubility, optimum pharmacokinetics and decreased toxicity. These naturally occurring molecules have therefore been extensively used to access diverse library of compounds with great chemotherapeutic importance. This review highlights an overview of development of carbohydrate-based molecules from others and our lab which have shown promising biological activity against front line diseases.

Synthesis and evaluation of small libraries of triazolylmethoxy chalcones, flavanones and 2-aminopyrimidines as inhibitors of mycobacterial FAS-II and PknG

A synthetic strategy to access small libraries of triazolylmethoxy chalcones 4{1-20}, triazolylmethoxy flavanones 5{1-10} and triazolylmethoxy aminopyrimidines 6{1-17} from a common substrate 4-propargyloxy-2-hydroxy acetophenone using a set of different reactions has been developed. The chalcones and flavanones were screened against mycobacterial FAS-II pathway using a recombinant mycobacterial strain, against which the most potent compound showed ∼88% inhibition in bacterial growth and substantially induction of reporter gene activity at 100 μM concentration. The triazolylmethoxy aminopyrimdines were screened against PknG of Mycobaceterium tuberculosis displaying moderate to good activity (23-53% inhibition at 100 μM), comparable to the action of a standard inhibitor.

One pot efficient diversity oriented synthesis of polyfunctional styryl thiazolopyrimidines and their bio-evaluation as antimalarial and anti-HIV agents.

An efficient one pot synthesis of a series of pluripotent (E)-1-(3-methyl-5-aryl-7-styryl-5H-thiazolo[3,2-a]pyrimidin-6-yl)-3-arylprop-2-en-1-ones is reported. It involves reaction of 5-acetyl-6-methyl-4-aryl-dihydropyrimidine-2-thiones, propargyl bromide and aromatic aldehydes in presence of ethanolic KOH. The newly synthesized compounds were evaluated for antimalarial activity against Plasmodium falciparum and as HIV-RT inhibitors. Most of the compound displayed potent antimalarial activity with IC(50)<2 μg/mL. Compounds 6, 11 and 20 showed better activity against P. falciparum K1 strains in comparison to standard drug chloroquine. Compounds 6, 11, and 16 exhibited 73.44, 66.92, and 70.81% HIV-RT inhibition at 100 μg/mL.

Aldol reaction of β-C-glycosylic ketones: synthesis of C-(E)-cinnamoyl glycosylic compounds as precursors for new biologically active C-glycosides

A series of beta-C-glycosylic ketones were prepared starting from d-glucose, d-xylose, d-mannose, and cellobiose. The beta-C-glycosylic ketones on aldol condensation with different aromatic aldehydes in the presence of a suitable organocatalyst led to the formation of respective C-(E)-cinnamoyl glycosides stereoselectively in good yields as precursors for the synthesis of biologically active compounds.

Robust Turn Structures in α3β Cyclic Tetrapeptides Induced and Controlled by Carbo-β3 Amino Acid

Designing cyclic tetrapeptides (CTPs), which fold into desired structures, is often a challenging task. While it is difficult to synthesize them, they are also prone to adopt multiple conformations. In this paper we report the synthesis and conformational studies of CTP mimics, having nonconstrained α(3)β motif, that exhibit stable β- and γ-turn structures. We also demonstrate the transformation of β-turn to γ-turn structure in similar CTPs by inverting the chirality of β(3) carbon in C-linked-carbo-β(3)-amino acid (Caa) from R to S.

Solution-Phase Synthesis of a Library of Carbapeptide Analogues Based on Glycosylamino Acid Scaffolds and Their In Silico Screening and Antimicrobial Evaluation

A well-organized and efficient approach toward the solution phase synthesis of a library of carbapeptide analogues based on glycosyl amino ester scaffold is described. The reported synthetic route involves a five step preparation of heptofuranuronamides 6a-h and octopyranuronamide 7e from glycosyl amino esters 1 and 7, respectively. Coupling of glycosyl amino esters 1 or 7 with three different N-Fmoc protected amino acids afford the N-Fmoc protected intermediates 2a-c and 7a. Deprotection of Fmoc group in 2a-c and 7a with piperidine gave respective compounds 3a-c and 7b with free amine. Subsequent coupling of 3a-c and 7b with different aromatic acids furnishes respective heptofuranuronates 4a-h and octopyranuronate 7c in good yields. The latter, on ester hydrolysis by LiOH gave the corresponding glycopeptide analogues 5a-h and 7d with terminal carboxyl group. The carboxyl group in these compounds was amidated with oxalyl chloride/ NH(4)OH to afford heptofuranuronamides 6a-h and octopyranuronamides 7e. In vitro screening of all compounds displayed moderate antifungal, antitubercular, and general antibacterial activities. Reverse docking calculations involving over 841 protein drug targets have identified two potential targets for these compounds. These results will form the basis for synthesizing second-generation antimicrobial compounds.

A Novel Approach for Clustering Web User Sessions Using RST

Web usage mining has assumed importance in learning about web user’s behavior and user interactions with the website. It uses data mining techniques to discover non-trivial user behavior patterns. These patterns can then be used to make the predictions of next page to be accessed by the user. This paper proposes a novel approach for preprocessing wherein rough set clustering is applied to form the clusters of sessions. These sessions could later on be used to form the knowledge base of rules on the basis of which the next page to be accessed could be prefetched.

A convenient synthesis of novel pyranosyl homo-C-nucleosides and their antidiabetic activities

A series of pyranosyl homo-C-nucleosides have been synthesized by reaction of butenonyl C-glycosides (5a-5j, and 8) and cyanoacetamide in presence of t-BuOK followed by further modifications. The reaction proceeds by Michael addition of cyanoacetamide to the butenonyl C-glycosides and subsequent dehydrative cyclization and oxidative aromatization to give glycosylmethyl pyridones (6a-6j, 7a-7j, 9, and 10). The glycosylmethyl pyridones (6a-6e) on reaction with POCl(3) under reflux gave respective glycosylmethyl pyridines (11a-11e and 12a-12e) in good yields. The synthesized compounds were screened for their in vitro α-glucosidase, glucose-6-phosphatase and glycogen phosphorylase inhibitory activities. One of the pyridylmethyl homo-C-nucleoside, compound 11d, displayed 52% inhibition of glucose-6-phosphatase as compared to the standard drug sodium orthovanadate while compound 12a showed a significant antihyperglycemic effect of 17.1% in the diabetic rats as compared to the standard drug metformin.

A Novel Approach for Determining Next Page Access

Reduction of World Wide Web user perceived latency has assumed importance in the wake of the fast development of Internet services and a huge amount of network traffic and hence adaptation of Web pages to the needs of a specific user is todays trend of Web technologies. Although Web performance can be improved by caching, the benefit of using it is rather limited owing to filling the cache with documents without any prior knowledge. Web prefetching becomes an attractive solution wherein forthcoming page accesses of a client are predicted, based on access log information. This paper proposes a Zipfpsilas Law based novel approach for the determination of next page likely to be accessed by specific client.

Ontology Driven Query Expansion for Better Image Retrieval

As more information becomes available on the Web it is more difficult to provide effective search services for Internet users. Since, it is assumed that users do not always formulate search queries using the best terms. So, search engines invoke query expansion to increase the quality of user search results. Query expansion is useful in reducing query/document mismatch by expanding the query using words or phrases with a similar meaning or some other statistical relation to the set of relevant documents. This paper proposes an approach for ontology driven query expansion for better image retrieval. In this work the association rules; generated by mining web logs and WorldNet have been used for query expansion process. Further, an algorithm has been proposed and the performance has been measured.