Sanjeev Kanojiya

Cassane Diterpenes from Caesalpinia bonduc.

Three cassane diterpene hemiketals, caesalpinolide-C, caesalpinolide-D, caesalpinolide-E and one cassane furanoditerpene were isolated from Caesalpinia bonduc. The molecular structures were elucidated using NMR spectroscopy in combination with IR, UV and mass spectral data and relative stereochemistries were determined through ROESY correlation. The isolated compounds were tested for their antiproliferative activity against MCF-7 (breast adenocarcinoma), DU145 (prostate carcinoma), C33A (Cervical carcinoma) and Vero (African green monkey kidney fibroblast) cells.

Antiproliferative action of Xylopia aethiopica fruit extract on human cervical cancer cells.

The anticancer potential of Xylopia aethiopica fruit extract (XAFE), and the mechanism of cell death it elicits, was investigated in various cell lines. Treatment with XAFE led to a dose‐dependent growth inhibition in most cell lines, with selective cytotoxicity towards cancer cells and particularly the human cervical cancer cell line C‐33A. In this study, apoptosis was confirmed by nuclear fragmentation and sub‐G0/G1 phase accumulation. The cell cycle was arrested at the G2/M phase with a decreased G0/G1 population. A semi‐quantitative gene expression study revealed dose‐dependent up‐regulation of p53 and p21 genes, and an increase in the Bax/Bcl‐2 ratio. These results indicate that XAFE could be a potential therapeutic agent against cancer since it inhibits cell proliferation, and induces apoptosis and cell cycle arrest in C‐33A cells. Copyright

Synthesis of 3,4,5‐Trisubstituted Isoxazoles from Morita–Baylis–Hillman Acetates by an NaNO2/I2‐Mediated Domino Reaction

An efficient NaNO2 /I2 -mediated one-pot transformation of Morita-Baylis-Hillman (MBH) acetates into alkyl 3-nitro-5-(aryl/alkyl)isoxazole-4-carboxylates is described. In a cascade event, initial Michael addition of NaNO2 to the MBH acetate furnishes the allylnitro intermediate which undergoes I2 -catalyzed oxidative α-CH nitration of the nitromethyl subunit followed by [3+2] cycloaddition to afford the title compounds. Structural elaborations of these highly substituted isoxazoles by SN Ar reactions and hydrogenolysis allows access to useful products.

Cytotoxic cycloartane triterpene and rare isomeric bisclerodane diterpenes from the leaves of Polyalthia longifolia var. pendula.

A 24-methylenecycloartane-3 β, 16 β, 23 β-triol, Longitriol (1), rare bisclerodane imides, Longimide A (2) and previously known Longimide B (3) were isolated from ethanolic extract of the leaves of Polyalthia longifolia var. pendula. This is the first example of isolation of any cycloartane triterpene from this plant source. Structures were determined by extensive (1D and 2D NMR) spectroscopic data analysis combined with ESI MS/MS fragmentation and X-ray analysis. Furthermore, Compounds 1 and 2 were evaluated for their cytotoxic effects against four human cancer cell lines and found to be most active against cervical carcinoma cell lines with IC(50) value of 10.03 and 4.12 μg/mL, respectively.

Pd-Catalyzed Isocyanide Assisted Reductive Cyclization of 1-(2-Hydroxyphenyl)-propargyl Alcohols for 2-Alkyl/Benzyl Benzofurans and Their Useful Oxidative Derivatization

An unusual Pd-catalyzed isocyanide assisted 5-exo-dig reductive cyclization of 1-(2-hydroxyphenyl)-propargyl alcohols is achieved for 2-alkyl/benzyl benzofurans. The reaction features a high substrate scope, insensitivity to air, and excellent product yielding. Further, a direct metal-free C-H functionalization (azidation, alkoxylation, and hydroxylation) and selective oxidative cleavage of thus synthesized 2-benzylfurans are described for azido-, alkoxy-, hydroxyl-, amide-, and tetrazolyl adducts.

Synthesis and antimalarial activity of 3,3-spiroanellated 5,6-disubstituted 1,2,4-trioxanes.

Novel 3,3-spiroanellated 5-aryl, 6-arylvinyl-substituted 1,2,4-trioxanes 19-34 have been synthesized and appraised for their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice by oral route at doses ranging from 96 mg/kg × 4 days to 24 mg/kg × 4 days. The most active compound of the series (compound 25) provided 100% protection at 24 mg/kg × 4 days, and other 1,2,4-trioxanes 22, 26, 27, and 30 also showed promising activity. In this model, β-arteether provided 100 and 20% protection at 48 mg/kg × 4 days and 24 mg/kg × 4 days, respectively, by oral route. Compound 25 displayed a similar in vitro pharmacokinetic profile to that of reference drug β-arteether. The activity results demonstrated the importance of an aryl moiety at the C-5 position on the 1,2,4-trioxane pharmacophore.

Rapid identification of calotropagenin glycosides using high-performance liquid chromatography electrospray ionisation tandem mass spectrometry.

INTRODUCTION Cardiac glycosides in Calotropis procera have therapeutic use as inhibitors of Na⁺/K⁺-ATPase to regulate heart contractions. A large amount of research attention has been received by these compounds towards their identification and structural characterisation. In order to achieve rapid identification of cardiac glycosides in phytochemical extracts a liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed involving metal cationisation by post-column addition of alkali salts for the unambiguous determination of their molecular weights. OBJECTIVE Identification of cardiac glycosides in Calotropis procera leaf extract. RESULTS Calotropagenin and its 10 glycosides were unambiguously identified. The daughter ions at m/z 387, 369, 359, 351, 341 and 323 in their MS/MS spectra were attributed to the calotropagenin aglycone unit. CONCLUSION High performance liquid chromatography in combination with electrospray ionization tandem mass spectrometry involving metal cationisation by post column addition of alkali salts was successfully utilised for the rapid identification of calotropagenin glycosides/derivatives in Calotropis procera extract.

Naturally Occurring Carbazole Alkaloids from Murraya koenigii as Potential Antidiabetic Agents

This study identified koenidine (4) as a metabolically stable antidiabetic compound, when evaluated in a rodent type 2 model (leptin receptor-deficient db/db mice), and showed a considerable reduction in the postprandial blood glucose profile with an improvement in insulin sensitivity. Biological studies were directed from the preliminary in vitro evaluation of the effects of isolated carbazole alkaloids (1-6) on glucose uptake and GLUT4 translocation in L6-GLUT4myc myotubes, followed by an investigation of their activity (2-5) in streptozotocin-induced diabetic rats. The effect of koenidine (4) on GLUT4 translocation was mediated by the AKT-dependent signaling pathway in L6-GLUT4myc myotubes. Moreover, in vivo pharmacokinetic studies of compounds 2 and 4 clearly showed that compound 4 was 2.7 times more bioavailable than compound 2, resulting in a superior in vivo efficacy. Therefore, these studies suggested that koenidine (4) may serve as a promising lead natural scaffold for managing insulin resistance and diabetes.

Fragmentation patterns of newly isolated cassane butenolide diterpenes and differentiation of stereoisomer by tandem mass spectrometry

Different stereoisomers of active molecules often cause different physiological responses and hence pose a challenge for their identification. This study involves perceptive fragmentation behavior of newly isolated cassane butenolides, caesalpinolide A [1] and caesalpinolide B [2] (epimeric at the hemiketal position) by tandem MS. The electrospray ionization-mass spectrometry (ESI-MS)/collision-induced dissociation (CID; ESI-MS(2) and ESI-IT-MS(n)) were investigated. The effect of orientations of hemiketal hydroxyl at C-12 was clearly observed in the mass spectrum. Tandem mass spectra of 1, 1(A) or 2, 2(A) show stereospecific fragmentation resulting in significant abundance dissimilarity of [MH - H(2)O](+) as well as differences in fragmentation pathway. Both of these pathways seem to be influenced by the stereochemistry of the molecule. The differentiation can be clearly visualized from the [M + H - H(2)O](+)/[M + H](+) ratio of the two isomers where beta-isomer 2 was found to be five times higher than that of alpha-isomer 1 in full scan liquid chromatography-electrospray ionization mass spectrometry(LC-ESI-MS). In high-energy CID, the mass fingerprint of 1, 2, 1(A), and 2(A) was found to be different from one another.

Pharmacokinetic and metabolism studies of rohitukine in rats by high performance liquid-chromatography with tandem mass spectrometry

A sensitive, selective, and rapid high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the quantification of rohitukine in rat plasma. HPLC was performed using a Symmetry-Shield C18 (5 μ, 4.6 × 150 mm) column, and isocratic elution with ammonium acetate buffer (pH4; 10 mM):methanol (08:92, v/v) at a flow rate of 0.6 mL/min. Sample clean-up involved solid phase extraction (SPE) of analyte and internal standard (phenacetin) from 100 μL plasma. The parent→product ion transitions (MRM) for analyte and IS were 306.1→245.1 m/z and 180.1→138.1 m/z respectively, and were monitored on a triple quadrupole mass spectrometer, operating in positive ion mode. The method was validated across the dynamic concentration range of 5-500 ng/mL for rohitukine, with a fast run time of 4.5 min. The analytical method measured concentrations of rohitukine with accuracy (% bias) of <±10% and precision (% RSD) of <±12%. Rohitukine was stable during the battery of stability studies viz., bench-top, auto-sampler, freeze/thaw cycles and 30 days of storage in a freezer at -70±10°C. Finally, the applicability of this assay has been successfully demonstrated in vivo pharmacokinetic and in vitro metabolism studies in Sprague-Dawley rat. This method will therefore be highly useful for future preclinical and clinical pharmacokinetic studies of rohitukine.