Sukdeb Banerjee

Synthesis of a novel quinoline derivative, 2-(2-methylquinolin-4-ylamino)-N-phenylacetamide—a potential antileishmanial agent

Some novel quinoline derivatives were prepared and tested for antileishmanial activity. 2-(2-Methylquinolin-4-ylamino)-N-phenylacetamide (2) was found to be significantly more active than the standard antileishmanial drug sodium antimony gluconate (SAG) in reducing the parasite load both in the spleen and liver at a much lower concentration in hamster models. The results suggest that the compound could be exploited as an antileishmanial drug.

Polyoxypregnane glycosides from the flowers of Dregea volubilis.

Three novel polyoxypregnane glycosides, volubiloside A, B and C (1-3), were isolated from the flowers of Dregea volubilis Linn., and their structures were elucidated as drevogenin D-3-O-beta-D-glucopyranosyl (1-->4)-6-deoxy-3-O-methyl-beta-D-allopyranosyl (1-->4)-beta-D-cymaropyranosyl (1-->4)-beta-D-cymaropyranoside, drevogenin D-3-O-beta-D-glucopyranosyl (1-->4)-6-deoxy-3-O-methyl-beta-D-allopyranosyl (1-->4)-beta-D-cymaropyranosyl (1-->4)-beta-D-digitoxopyranoside and drevogenin P-3-O-beta-D-glucopyranosyl (1-->4)-6-deoxy-3-O-methyl-beta-D-allopyranosyl (1-->4)-beta-D-cymaropyranosyl (1-->4)-beta-D-cymaropyranoside, respectively, on the basis of extensive NMR experiments, MALDI-TOF MS, and some chemical strategies.

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.

Metabolism of progesterone and testosterone by a Bacillus sp.

Microbial transformations by a Bacillus sp. were employed as a means of preparing potentially important derivatives of progesterone and testosterone. Each microbial metabolite was subjected to structure elucidation employing 1H and 13C nmr, mass spectral and cd analysis. Hplc was used for the determination of the percentages of the metabolites formed. The progesterone metabolites were characterised as 14-hydroxy-4-pregnene-3,20-dione (II), 14-hydroxy-5 alpha -pregnane-3,6,20-trione (III), 11 alpha-hydroxy-5 alpha-pregnane-3, 6,20-trione (IV) and 11 alpha,14-dihydroxy-4-pregnene-3,20-dione (V). The testosterone analogs were identified as 4-androstene-3,17-dione (VII), 17 beta-hydroxy-5 alpha-androstane-3,6-dione (VIII), 14-hydroxy-4-androstene-3,17-dione (IX) and 14, 17 beta-dihydroxy-4-androsten-3-one (X). The availability of the metabolites enabled complete elucidation of their 13C nmr spectra.

Determination of drug-like properties of a novel antileishmanial compound: In vitro absorption, distribution, metabolism, and excretion studies

In drug discovery research, the compounds should not only to be potent and selective but also must possess acceptable pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) to increase success rate in clinical studies. Objective: Exploration of drug-like properties of 2-(2-methylquinolin-4-ylamino)-N-phenyl acetamide, a potent antileishmanial compound by performing some in vitro ADME experiments along with validation of such studies. Materials and Methods: Experimental protocols were established and validated for stability (in PBS pH7.4, simulated gastric and intestinal fluid), solubility, permeability, distribution coefficient (Log D), plasma protein binding and metabolism by rat liver microsomes by using spectrophotometer or HPLC. Methods were considered valid if the results of the standard compounds matched with reported results or within acceptable range or with proper ranking (high-medium-low). Results: The compound was found to be stable (>95% remaining) in all stability studies and aqueous solubility was 299.7 ± 6.42 μM. The parallel artificial membrane permeability assay (PAMPA) indicated its medium permeability (Log Pe = −5.53 ± 0.01). The distribution coefficients (Log D) in octanol/PBS and cyclohexane/PBS systems were found to be 0.54 and −1.33, respectively. The plasma protein binding study by the equilibrium dialysis method was observed to be 78.82 ± 0.13% while metabolism by Phase-I enzymes for 1 hour at 37°C revealed that 36.07 ± 4.15% of the compound remained after metabolism. Conclusion: The methods were found to be very useful for day-to-day ADME studies. All the studies with the antileishmanial compound ascertained that the compound bears optimum pharmacokinetic properties to be used orally as a potential drug for the treatment of leishmaniasis.

Triterpene glycosides from the bark of Anthocephalus cadamba

Two triterpenoid glycosides, glycosides A and B were isolated from the bark of Anthocephalus cadamba and defined as 3-O-[α-L-rhamnopyranosyl]-quinovic acid-28-O-[β-D-glucopyranosyl] ester and 3-O-[β-D-glucopyranosyl]-quinovic acid-28-O-[β-D-glucopyranosyl] ester respectively.

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.

Chenopodium album seed extract-induced sperm cell death: exploration of a plausible pathway

BACKGROUND This study was conducted for to explore the plausible pathway of Chenopodium album seed extract (CAE)-mediated sperm cell death. STUDY DESIGN The role of CAE for its spermicidal action was assessed by (a) measuring lipid peroxidation, protein carbonyl content and intracellular glutathione content in CAE exposed sperm cells; (b) assaying antioxidant enzymes like catalase and superoxide dismutase (SOD); (c) analyzing protein expressions by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis; (d) fluorimetric measurement of intracellular H(2)O(2) level and generation of reactive oxygen species (ROS) in CAE-treated sperm cells; and (e) DNA ladder formation study. RESULTS CAE-induced sperm death is due to (a) lipid peroxidation of the sperm cell membrane, oxidation of some critical cellular proteins and depletion of intracellular reduced gluthathione, indicating production of ROS; (b) activation of Mn-SOD and inactivation of catalase favoring endogenous accumulation of H(2)O(2); (c) generation of O(2)(*-) at an enhanced rate during oxidative stress as evidenced by increased Mn-SOD activity and protein expression; (d) accumulation of ROS in spermatozoa reflected in the fluorimetric experiments; and (e) increased production of O(2)(*-) and H(2)O(2) induced apoptosis-like death in sperm cells as observed by DNA ladder formation. CONCLUSION The sperm death mediated by CAE is due to oxidative damage of cellular macromolecules by in situ generation of ROS.

Metabolism of progesterone by Aspergillus fumigatus

Abstract Metabolism of progesterone by a typical strain of Aspergillus fumigatus was studied. The four metabolites isolated were characterized as 5α-pregnane-3s-ol-20-one, 15s-hydroxy-1,4-pregnadiene-3,20-dione, 7s,15s-dihydroxy-4-pregnene-3,20-dione and 11α,15s-dihydroxy-4-pregnene-3,20-dione by the application of various spectrometric techniques.

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.