Asish K. Bhattacharya

Diversity-oriented synthesis of α-aminophosphonates: a new class of potential anticancer agents.

A small library of structurally diverse α-aminophosphonates has been synthesized by reacting alkyl/aryl aldehydes, alkyl/aryl amines and alkyl/aryl phosphites in one-pot catalyzed by Amberlite-IR 120 resin (acidic). All the synthesized α-aminophosphonates were assayed for their in vitro cytotoxic activities against a panel of five human cancer cell lines including A-549, NCI-H23 (Lung), Colo 320DM (Colon), MG-63 (Bone marrow) and Jurkat (Blood T lymphocytes). Compound 4n having (R)-1-phenylethanamine was found to be the most active amongst all the synthesized α-aminophosphonates against all the five cancer cell lines, most prominent being against Jurkat cell line with an IC50 value of 4 μM. Surprisingly, compound 4o having (S)-1-phenylethanamine was found to be devoid of any cytotoxicity. Our finding suggests that these chemical entities could further serve as interesting template for the design of potential anticancer agents.

An efficient synthesis of a hydroxyethylamine (HEA) isostere and Its α-aminophosphonate and phosphoramidate derivatives as potential anti-HIV agents

HIV protease is a promising drug target for AIDS therapy, and several potent HIV‐1 protease inhibitors have been reported to date. Although existing inhibitors exhibit high selectivity, they have also been associated with severe side effects and the possible emergence of therapeutic resistance. As HIV protease cleaves the peptide bond via a tetrahedral intermediate, various transition‐state models such as hydroxyethylamine (HEA) have been designed. We therefore pursued an efficient synthesis of an HEA isostere; this was performed with a novel one‐pot reduction–transimination–reduction reaction sequence as a key step. α‐Aminophosphonate and phosphoramidate derivatives of the HEA isostere were designed and synthesized, and all of the synthesized derivatives were assayed for their anti‐HIV activities against wild‐type and mutant HIV strains. Phosphoramidate derivative 15 a was found to be the most active of all synthesized compounds against the IIIB and RES056 strains. As phosphonates are known to exhibit physiological stability, good cell permeability, and other promising pharmacokinetic characteristics, our newly synthesized compounds have the potential as alternatives to existing therapeutics and diagnostics.

Clerodane type diterpene as a novel antifungal agent from Polyalthia longifolia var. pendula

Bioactivity-guided chemical examination of methanolic extract of leaves of Polyalthia longifolia var. pendula led to the isolation of the active constituent, a diterpene 1 which was identified as 16α-hydroxycleroda-3,13(14)Z-dien-15,16-olide on the basis of its spectral data. Among the tested strains, diterpene 1 was found to exhibit antifungal activities having MIC90 values of 50.3, 100.6 and 201.2 μM against Candida albicans NCIM3557, Cryptococcus neoformans NCIM3542 (human pathogens) and Neurospora crassa NCIM870 (saprophyte), respectively. Initial, structure-activity-relationship (SAR) data generated by synthesizing some derivatives revealed that the double bond between C3-C4 and the free hydroxyl group at C16 are crucial for the antifungal activity of the diterpene 1. The mode of action of 1 in C. albicans is due to compromised cell membrane permeability and also probably due to disruption of cell wall structures. The red blood cell haemolysis of all the compounds (1-4) did not show any significant haemolysis and was found to be less than 15% for all the compounds when tested at highest concentration, i.e. 1200 μM. Interestingly, all the tested compounds inhibited Y-H transition in dimorphic C. albicans NCIM3557 at much lower concentration than their MIC90 values. Determination of ROS generation by diterpene 1 using DCFH-DA and DHR123 (dihydrorhodamine) staining of C. albicans NCIM3557 indicated production of intracellular ROS as a mechanism of antifungal activity.

Design, synthesis and biological evaluation of peptidyl-vinylaminophosphonates as novel cysteine protease inhibitors.

We report herein, design and synthesis of vinylaminophosphonates, a novel class of compounds as possible cysteine protease inhibitors. The synthesis of vinylaminophosphonates has been accomplished employing Tsuji-Trost reaction as a key step. The synthesized compounds were assayed against papain, a model cysteine protease and some of our synthesized compounds showed IC(50) values in the range of 30-54 μM thereby suggesting that these chemical entities thus could constitute an interesting template for the design of potential novel protease inhibitors.

Design and synthesis of aryl/hetarylmethyl phosphonate-UMP derivatives as potential glucosyltransferase inhibitors

Abstract A novel class of glucosyltransferase inhibitors has been designed and synthesised. The designed inhibitors 1 – 4 provide conformational mimicry of the transition-state in glucosyltransfer reactions. The key synthetic steps involve a Michaelis–Arbuzov reaction followed by coupling with uridine-5′-morpholidophosphate as activated UMP derivative.

SAR directed design and synthesis of novel β(1-4)-glucosyltransferase inhibitors and their in vitro inhibition studies

This paper describes SAR directed design and synthesis of novel beta(1-4)-glucosyltransferase (BGT) inhibitors. The designed inhibitors 1-5 provide conformational mimicry of the transition-state in glucosyltransfer reactions. The compounds were tested for in vitro inhibitory activity against (BGT) and the inhibition kinetics were examined. Three of the designed molecules were found to be potential inhibitors of BGT having IC50 values in micromolar (microM) range. Useful structure-activity relationships were established, which provide guidelines for the design of future generations of inhibitors of BGT.

Biomimetic Total Synthesis of Angiopterlactone B and Other Potential Natural Products

A one-pot biomimetic synthesis of (-)-angiopterlactone B and its enantiomer (+)-angiopterlactone B has been accomplished via TBAF-catalyzed tandem ring contraction followed by oxa-Michael/Michael addition sequence. Comparison of specific optical rotations, absolute configurations, and CD spectra of natural, synthesized (-)-angiopterlactone B and (+)-angiopterlactone B unequivocally proves that the isolated angiopterlactone B must be levorotatory. Synthesis of hitherto undiscovered natural products 18 and 20 and analogues of angiopterlactone B demonstrate the versatility of this method.

Direct Glycosylation of Unprotected and Unactivated Sugars Using Bismuth Nitrate Pentahydrate

GRAPHICAL ABSTRACT Bi(NO3)3, a low-cost, mild, and environmentally green catalyst, has been successfully utilized for Fischer glycosylation for the synthesis of alkyl/aryl glycopyranosides by reacting unprotected sugars, namely, D-glucose, L-rhamnose, D-galactose, D-arabinose, and N-acetyl-D-glucosamine with various alcohols in good to excellent yields. The glycosides were formed with high α-selectivity. Further, an expedient separation of α- and β-glycosides using silver nitrate–impregnated silica gel flash liquid chromatography has been developed.

Efficient Bakers’ Yeast-Catalyzed Multicomponent Synthesis of α-Aminophosphonates in One Pot

Abstract Utilizing bakers’ yeast (Saccharomyces cerevisiae) as a biocatalyst, synthesis of α-aminophosphonates in one pot has been accomplished by the three-component reaction of an aldehyde, an amine, and diethyl phosphite in moderate to good yields under solvent-free reaction conditions. Supplemental materials are available for this article. Go to the publishers online edition of Synthetic Communications® to view the free supplemental file. GRAPHICAL ABSTRACT

Patho-physiological evaluation of Duranta erecta for the treatment of urolithiasis

Background Urolithiasis is the third common disorder of the urinary system affecting 10–15% of the general population. In recent years, search for new antilithiatic drugs from natural sources has assumed greater importance. Objectives This study was performed to investigate the anti-urolithiatic activity of methanolic extract of Duranta erecta leaves by in vitro and in vivo analysis. Materials and methods The study was designed to determine presence of phytochemicals in D. erecta, its yield in percentage, antioxidant activity against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and anti-microbial property against few bacteria. In vitro analysis was carried out study anti-urolithiatic property of D. erecta by nucleation assay and synthetic urine assay for inhibition of calcium oxalate and calcium oxalate monohydrate crystals formation. An in vivo experiment was performed on Wistar rats for confirmation of anti-urolithiatic property of D. erecta in animal model. Results D. erecta has the presence of primary and secondary metabolites like glycoside, saponins, sterols, flavonoids, phenols, tannins, alkaloids, carbohydrates and proteins. Methanolic extract of D. erecta gave a very good yield (60%). D. erecta proved its antioxidant potential by 93.51% inhibition of DPPH radical at a concentration of 1000 μg/mL where ascorbic showed 94.71% of DPPH radical at the same concentration. In vitro tests like nucleation assay and synthetic urine assay showed that D. erecta inhibits formation of calcium oxalate and calcium oxalate monohydrate crystals. It also showed the anti-microbial property by formation of zone of inhibition against few bacteria. An in vivo experiment on Wistar rat animal model confirmed the anti-urolithiatic property of D. erecta L. leaves extract. Conclusions Based on the results, we reported that D. erecta may treat calcium oxalate crystal deposition in the kidney by preventing hyperoxaluria-induced peroxidative damage to the renal tubular membrane surface (lipid peroxidation). It has anti-microbial potential so it may also inhibit the secondary bacterial infection in kidney. Based on the data, it can be concluded that this herb can be used as a potential anti-urolithiasis agent for kidney stone removal.