K. J. Rajendra Prasad

In vivo anti-diabetic, antioxidant and molecular docking studies of 1, 2, 8-trihydroxy-6-methoxy xanthone and 1, 2-dihydroxy-6-methoxyxanthone-8-O-β-D-xylopyranosyl isolated from Swertia corymbosa.

1, 2, 8-trihydroxy-6-methoxy xanthone (1) and 1, 2- dihydroxy-6-methoxyxanthone-8-O-β-d-xylopyranosyl (2) are the main constituents of petroleum ether and ethyl acetate extracts from Swertia corymbosa (Gentinaceae), a medicinal plant used in Indian traditional system for the treatment of diabetes. The present study was designed to examine the antihypoglycemic, antihyperlipidemic and antioxidant effect of compounds 1 and 2 in streptozotocin (STZ) induced diabetic rats. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (60 mg/kg b.w.). The isolated compounds 1 and 2 at a dose of 50 mg/kg b.w., produced the maximum fall of 83% in the blood glucose level in the diabetic rats after 3h of the treatment. The administration of 1 and 2 (50 mg/kgb.w.) daily for 28 days in STZ induced diabetic rats, resulted in a significant decrease in blood glucose, glycosylated hemoglobin, SGOT, SGPT, ALP serum urea and creatinine with significant rise in plasma insulin level. Test compounds 1 and 2 showed antihyperlipidemic activities as evidenced by significant decrease in serum TC, TG, LDL-C, VLDL-C levels coupled together with elevation of HDL-C level in diabetic treated rats when compared to diabetic untreated rats, indicate the protective role against liver and kidney damage. The results of histopathology also showed 1 and 2 protected tissues (pancreas, liver and kidney) against peroxidation damage and maintained tissue integrity. Further, the molecular interaction study of the ligands 1, 2 and glibenclamide with various diabetes mellitus related protein targets like glucokinase (PDB ID: 1V4S), fructose-1, 6-bisphosphatase 1 (PDB ID: 2JJK) 11-β-hydroxysteroid dehydrogenase (PDB ID: 2BEL) and modeled protein sulfonylurea receptor 1 (SUR1) showed that ligand 1 and 2 possess binding affinity with all protein targets except for 2BEL target protein for which ligand 1 has no interaction. The ligand pose with 2BEL and SUR1 protein target of ligand 2 gave the best binding conformation. Hence 1 and 2 can be considered for developing into a potent antidiabetic drug.

l-Proline anchored multicomponent synthesis of novel pyrido[2,3-a]carbazoles; investigation of in vitro antimicrobial, antioxidant, cytotoxicity and structure activity relationship studies

The newly synthesized pyrido[2,3-a]carbazoles were prepared in good yields by multicomponent reactions under L-proline as promoter and structurally characterized. Few compounds showed significant activity toward both gram-positive, gram-negative bacterial strains. All compounds exerted negative efficacy for antifungal activity except compounds 5f and 7f which showed moderate activity. All compounds showed weak to moderate capacity for scavenging DPPH. The cytotoxicity was evaluated by Sulforhodamine B assay against A-549, B16F10, HCT-15, SKMel2 and SKOV3 cell lines and compared with standard drug cisplatin. Compound 5f outperformed cisplatin against A-549, HCT-15, SKMel2 and B16F10 cell lines. Compound 5e outranged cisplatin against A-549, HCT-15, and SKMel2 cell lines. 5b outperformed cisplatin specifically against B16F10. The preliminary structure activity relationships were carried out.

Antiacetylcholinesterase and antioxidant ent -Kaurene diterpenoid, melissoidesin from Isodon wightii (Bentham) H. Hara

The ent kaurene diterpenoid, melissoidesin was isolated from the acetone extract of the leaves of Isodon wightii and the structure was designated as 3β, 11β, 15β-trihydroxy-6α-acetoxy-ent-kaur-16-ene based on spectral data and previous reports. Melissoidesin isolated from the acetone extract of leaves showed potent antiacetylcholinesterase activity and the IC50 value was observed as 215 µg mL−1. DPPH (1, 1-diphenyl-2-picrylhydrazyl) free radical scavenging activity of melissoidesin was significant and the IC50 value was 138 µg mL−1. The significant reducing property of the melissoidesin was stronger in high concentration. IC50 value of melissoidesin on hydroxyl radicals and metal chelation was observed as 99 and 143 µg mL−1, respectively. The 50% inhibitory concentration of melissoidesin on lipid peroxidation was calculated as 133 µg mL−1. These findings indicate that ent kaurene diterpenoid, melissoidesin was promising antiacetylcholinesterase and antioxidant which can be used as food and drug preparations.

Synthesis of hetero annulated carbazoles: exploration of in vitro cytotoxicity and molecular docking studies

The newly synthesized hetero annulated carbazoles were prepared in good yields and structurally characterized by all spectral means. The in vitro cytotoxicity was evaluated for all the synthesized compounds by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against HeLa and MCF 7 and compared with the standard drug ellipticine. Compound 5b outperformed the standard drug ellipticine. All the compounds showed moderate to potent activity against the cell lines. The preliminary structure–activity relationships were carried out. In order to understand the nature of interactions of these molecules we carried out molecular docking studies using the protein kinase CK2 inhibitors. The docking results provided some useful information for the future design of more potent inhibitors.

Synthesis of Novel Alkyl and Aryl Substituted Dibenzo[b,h][1,6]naphthyridines

Abstract A one-pot synthesis of 7-alkyl and aryl substituted dibenzo[b,h][1,6]naphthyridines is reported from the reaction of 4-chloro-2-methylquinolines and alkyl/aryl substituted aminoketones. Because the yield of the dibenzonaphthyridines was poor, in an alternative method the title compounds were prepared from the 4-chloro-2-methylquinolines via anilinoquinolines as intermediates employing alkyl and aryl carboxylic acids, which improved yields. GRAPHICAL ABSTRACT

Synthesis, characterization and pharmacological activities of 5,6,11,12-tetrahydroindolo[2,3-a]carbazole derivatives

Abstract A series of new 5,6,11,12-tetrahydroindolo[2,3-a]carbazole derivatives (3a–h) was synthesized. Treatment of 8-methyl-1-oxo-1,2,3,4-tetrahydrocarbazole (1a) with phenylhydrazine hydrochloride in ethanol furnished the title compound (3a) in poor yield along with 8-methyl-1-phenylhydrazono-1,2,3,4-tetrahydrocarbazole (2a). Better yields were obtained when 1a–h were treated with phenylhydrazine in glacial acetic acid. All the newly synthesized compounds were characterized on the basis of IR, NMR, mass-spectra and elemental analysis and screened for pharmacological activities.

Synthesis of Alkyl and Aryl Substituted Benzo[h]Naphtho[1,2-b][1,6]naphthyridines

Abstract The reaction of 4-chloro-2-methylquinolines and 1-naphthylamine under neat conditions yielded 2-methyl-N-(1-naphthyl)quinolin-4-amines. These potential intermediates on reaction with aliphatic and aromatic carboxylic acids yielded the respective 7-alkyl and -aryl substituted benzo[h]naphtho[1,2-b][1,6]naphthyridines. The highly deshielded protons in the final compounds were assigned on the basis of 2D NMR studies. GRAPHICAL ABSTRACT

9-Ethyl-N-(3-nitro­benzyl­idene)-9H-carbazol-3-amine

The title compound, C21H17N3O2, crystallizes with two molecules in the asymmetric unit. The carbazole groups show relatively small deviations from planarity [maximum displacements from the mean carbazole plane are 0.077 (7) and 0.101 (7) Å]. The dihedral angles between the 3-nitrobenzylideneamine and carbazole groups are 37.9 (1) and 37.0 (1)° in the two molecules.

Facile Synthesis of Alkyl and Aryl Substituted Dibenzo[b,g][1,8]naphthyridin-5-ones

The reaction of 2,4-dichloroquinolines with o-aminoacetophenone and o-aminobenzophenone under neat conditions yielded 2′-acetyl and 2′-benzoyl substituted-4-chloro-2-(N-phenylamino)quinolines, respectively, which on treatment with sodium methoxide afforded the 2′-substituted-4-methoxy-2-(N-phenylamino)quinolines. These potential intermediates, on polyphosphoric acid–catalyzed cyclization at two different temperatures, gave the respective 6-methyl and 6-phenyl substituted dibenzo[b,g][1,8]naphthyridin-5-ones. These temperature differences for the formation of the final products were due to the in situ formation of the respective 2′-substituted-2-(N-phenylamino)quinolin-4-ones from the chloro and methoxy intermediates. The naphthyridin-5-ones were subjected to N-methylation, where the methyl group in the 1-position was found to hinder the reaction sterically, consequently increasing the reaction time to more than that of the other derivatives.

New anthraquinones from Cassia obtusa

The isolation and spectral data of two new anthraquinones from Cassia obtusa roots are reported.