Abhijit Hazra

Regio- and Stereoselective Synthesis of a Library of Bioactive Dispiro-Oxindolo/Acenaphthoquino Andrographolides via 1,3-Dipolar Cycloaddition Reaction Under Microwave Irradiation

Dispiro-pyrrolidino/pyrrolizidino fused oxindoles/acenaphthoquinones have been derived from andrographolide via azomethine ylide cycloaddition to the conjugated double-bond under microwave (MW) irradiation. The reactions are chemo-, stereo-, and regioselective in nature. Change in amino acid from sarcosine/N-benzyl glycine to l-proline changes the regiochemistry. A representative library of 40 compounds along with in vitro anticancer evaluation is reported.

Basic alumina-supported highly effective Suzuki-Miyaura cross-coupling reaction under microwave irradiation: application to fused tricyclic oxa-aza-quinolones†

Basic alumina used in lieu of traditional mineral bases efficiently promotes a solvent free, Pd(PPh3)4 catalyzed Suzuki–Miyaura cross-coupling reaction under microwave irradiation.

Discovery of Safe and Orally Effective 4-Aminoquinaldine Analogues as Apoptotic Inducers with Activity against Experimental Visceral Leishmaniasis

ABSTRACT Novel antileishmanials are urgently required to overcome emergence of drug resistance, cytotoxic effects, and difficulties in oral delivery. Toward this, we investigated a series of novel 4-aminoquinaldine derivatives, a new class of molecules, as potential antileishmanials. 4-Aminoquinaldine derivatives presented inhibitory effects on L. donovani promastigotes and amastigotes (50% inhibitory concentration range, 0.94 to 127 μM). Of these, PP-9 and PP-10 were the most effective in vitro and demonstrated strong efficacies in vivo through the intraperitoneal route. They were also found to be effective against both sodium antimony gluconate-sensitive and -resistant Leishmania donovani strains in BALB/c mice when treated orally, resulting in more than 95% protection. Investigation of their mode of action revealed that killing by PP-10 involved moderate inhibition of dihydrofolate reductase and elicitation of the apoptotic cascade. Our studies implicate that PP-10 augments reactive oxygen species generation, evidenced from decreased glutathione levels and increased lipid peroxidation. Subsequent disruption of Leishmania promastigote mitochondrial membrane potential and activation of cytosolic proteases initiated the apoptotic pathway, resulting in DNA fragmentation and parasite death. Our results demonstrate that PP-9 and PP-10 are promising lead compounds with the potential for treating visceral leishmaniasis (VL) through the oral route.

Therapeutic effect of a novel anilidoquinoline derivative, 2-(2-methyl-quinoline-4ylamino)-N-(2-chlorophenyl)-acetamide, in Japanese encephalitis: correlation with in vitro neuroprotection.

2-(2-Methyl-quinoline-4ylamino)-N-(2-chlorophenyl)-acetamide, a novel anilidoquinoline derivative, was synthesised and evaluated for its therapeutic efficacy in treating Japanese encephalitis. The compound showed significant antiviral and antiapoptotic effects in vitro. Significant decreases in viral load (P<0.01) combined with an increase in survival was observed in Japanese encephalitis virus-infected mice treated with 2-(2-methyl-quinoline-4ylamino)-N-(2-chlorophenyl)-acetamide.

Synthesis of Bis-pyrrolizidine-Fused Dispiro-oxindole Analogues of Curcumin via One-Pot Azomethine Ylide Cycloaddition: Experimental and Computational Approach toward Regio- and Diastereoselection.

Curcumin has been transformed to racemic curcuminoids via an azomethine ylide cycloaddition reaction using isatin/acenaphthoquinone and proline as the reagents. The products were characterized by extensive 1D/2D NMR analysis and single-crystal X-ray crystallographic studies. The enantiomers of one racemic product were separated by HPLC on a Chiralcel OD-H column and were indeed confirmed by the CD spectra of the separated enantiomers.

NH 4 Cl-promoted synthesis of symmetrical and unsymmetrical triindolylmethanes under solvent-free conditions

The synthesis of various triindolylmethanes from indole-3-carboxaldehyde, using indole derivatives as reactants and NH4Cl as catalyst under solvent-free conditions, is described. This methodology provides access to both symmetrical and unsymmetrical triindolylmethanes in excellent yields. With N-methylindole particularly, indole-3-carboxaldehyde appears to act as a formyl donor, leading to the exclusive formation of a symmetrically trisubstituted product. The novelty of the methodology lies in its operational simplicity, environment friendly reaction conditions, and inexpensive and easy availability of the catalyst. A plausible mechanism of formation of the products is suggested.

Towards the Development of Anticancer Drugs from Andrographolide: Semisynthesis, Bioevaluation, QSAR Analysis and Pharmacokinetic Studies

Isolation of andrographolide from Andrographis paniculata, preparation of a library of derivatives via 1,3-dipolar cycloaddition of andrographolide with azomethine ylides generated from isatin derivatives or acenaphthoquinone and seconday α-amino acids, evaluation of the anticancer potential of the products, quantitative structure activity relationship studies and pharmacokinetic parameter determination have been described. 2D QSAR studies revaled that steric effects and van der Waals interactions play major roles in the determination of antiproliferative activity of these derivatives. 3D QSAR study predicted that the benzyl substitution at N20 position may be important for higher steric interaction. Pharmacokinetic studies with two most potent analogues revealed moderate chemical stability but poor aqueous solubility, metabolic stability and permeability with significant CYP3A4 inhibition.

Synthesis of symmetrically 1,4-disubstituted piperazine-2,5-diones : a new class of antileishmanial agents

A series of 1,4-diphenyl-2,5-dioxopiperazine derivatives were synthesised in one pot sequence. The compounds demonstrated appreciable cytotoxic activity against Leishmania donovani on both forms of the parasite, and the results suggested that some derivatives (4, 11 and 12) could be exploited as antileishmanial agents.

Tamarixetin 3-O-β-d-Glucopyranoside from Azadirachta indica Leaves: Gastroprotective Role through Inhibition of Matrix Metalloproteinase-9 Activity in Mice

Neem (Azadirachta indica) is a well-known medicinal and insecticidal plant. Although previous studies have reported the antiulcer activity of neem leaf extract, the lead compound is still unidentified. The present study reports tamarixetin 3-O-β-d-glucopyranoside (1) from a methanol extract of neem leaves and its gastroprotective activity in an animal model. Compound 1 showed significant protection against indomethacin-induced gastric ulceration in mice in a dose-dependent manner. Moreover, ex vivo and circular dichroism studies confirmed that 1 inhibited the enzyme matrix metalloproteinase-9 (MMP-9) activity with an IC50 value of ca. 50 μM. Molecular docking and dynamics showed the binding of 1 into the pocket of the active site of MMP-9, forming a coordination complex with the catalytic zinc, thus leading to inhibition of MMP-9 activity.

Aqueous phase supramoleculer synthesis of 3,2-and 3,3-dihetero-aromatic oxindoles catalysed by β-cyclodextrin

A high yielding green protocol is described for the synthesis of 3,2 and 3,3-diheteroaromatic oxindole involving the condensation of isatin with indole or pyrrole in an aqueous medium under neutral conditions by supramoleculer catalysis by β-cyclodextrin. The β-cyclodextrin can be easily recovered and reused without any loss of activity.