Kirpal S. Bisht

Phytochemistry of the genus Piper

Abstract The secondary metabolites isolated from Piper species for the period 1907 to June 1996 have been reviewed. Nearly six hundred chemical constituents belonging to different classes of bioactive compounds are listed together with their source(s) and references.

Review Article Number 138: Constituents of the yew trees

Yew trees, taxonomically classified under the genus Taxus, are sources of a number of physiologically active compounds of different classes. Taxane derivatives with various carbon skeletons, lignans, flavonoids, steroids and sugar derivatives have been isolated from different Taxus species. Compounds isolated from the genus Taxus between 1908 and December 1997 have been comprehensively reviewed.

Anti-invasive activity of alkaloids and polyphenolics in vitro

Invasiveness, the ability of certain tumour cells to migrate beyond their natural tissue boundaries, often leads to metastasis, and usually determines the fatal outcome of cancer. The need for anti-invasive agents has led us to search for possibly active compounds among alkaloids and polyphenolics. One hundred compounds were screened in an assay based on the confrontation of invasive human MCF-7/6 mammary carcinoma cells with fragments of normal embryonic chick heart in vitro. Anti-invasive activity was frequently found among chalcones having a prenyl group. Six compounds were found to inhibit invasion when added to the culture medium at concentrations as low as 1 microM. For at least three of them the anti-invasive effect could be associated with a cytotoxic effect on the MCF-7/6 cells, but not on the heart tissue. This selective cytotoxicity was substantiated by different methods, such as histology and growth assays (volume measurements, cell counts, MTT and sulforhodamine B assays). The anti-invasive effects of the compounds could neither be ascribed to induction of apoptosis nor to the promotion of cell-cell adhesion. Our data indicate that among the alkaloids and polyphenolics a number of molecules can inhibit growth and invasion of human mammary cancer cells via selective cytotoxicity.

Lignans and neolignans from Piper schmidtii

Abstract The unknown enantiomeric lignan (−)-machilin G and the known lignans (+)-calopiptin, (−)-zuionin A as well as a new neolignan kadsurin A and known neolignans futoquinol, isodihydrofutoquinol A, isodihydrofutoquinol B, along with parsley apiole, have been isolated from the leaves and stem of Piper schmidtii . The unpublished 13 C NMR data of the above known neolignans and the reassignment of the 1 H NMR spectrum of isodihydrofutoquinol B are also reported.

Functionalized polycarbonate derived from tartaric acid: enzymatic ring-opening polymerization of a seven-membered cyclic carbonate.

Enantiomerically pure functional polycarbonate was synthesized from a novel seven-membered cyclic carbonate monomer derived from naturally occurring L-tartaric acid. The monomer was synthesized in three steps and screened for polymerization with four commercially available lipases from different sources at 80 degrees C, in bulk. The ring-opening polymerization (ROP) was affected by the source of the enzyme; the highest number-average molecular weight, M(n) = 15500 g/mol (PDI = 1.7; [alpha]D(20) = +77.8, T(m) = 58.8 degrees C) optically active polycarbonate was obtained with lipase Novozyme-435. The relationship between monomer conversion, reaction time, molecular weight, and molecular weight distribution were investigated for Novozyme-435 catalyzed ROP. Deprotection of the ketal groups was achieved with minimal polymer chain cleavage (M(n) = 10000 g/mol, PDI = 2.0) and resulted in optically pure polycarbonate ([alpha]D(20) = +56) bearing hydroxy functional groups. Deprotected poly(ITC) shows T(m) of 60.2 degrees C and DeltaH(f) = 69.56 J/g and similar to that of the poly(ITC), a glass transition temperature was not found. The availability of the pendant hydroxyl group is expected to enhance the biodegradability of the polymer and serves in a variety of potential biomedical applications such as polymeric drug delivery systems.

Identification of a novel inhibitor of JAK2 tyrosine kinase by structure-based virtual screening

Janus kinase 2 (JAK2) plays a crucial role in the pathomechanism of myeloproliferative disorders and hematologic malignancies. A somatic mutation of JAK2 (Val617Phe) was previously shown to occur in 98% of patients with polycythemia vera and 50% of patients with essential thrombocythemia and primary myelofibrosis. Thus, effective JAK2 kinase inhibitors may be of significant therapeutic importance. Here, we applied a structure-based virtual screen to identify novel JAK2 inhibitors. One JAK2 inhibitor in particular, G6, demonstrated remarkable potency as well as specificity, which makes it as a potential lead candidate against diseases related to elevated JAK2 tyrosine kinase activity.

Novel chemoselective de-esterification of esters of polyacetoxy aromatic acids by lipases

Abstract Candida cylindracea lipase (CCL) and porcine pancreatic lipase (PPL) have been used for deacetylation of peracetates of methyl and ethyl esters of six different polyphenolic acids in organic solvents. Exclusive de-esterification of the ester groups derived from the phenolic hydroxy and aliphatic acid over the ester group of the aromatic acid and aliphatic alcohol has been achieved affording the corresponding esters of phenolic acids in as high yields as 90–97%. The results have been corroborated with the mechanism of lipase action.

Synthesis of novel bis- and tris-(cyclic carbonate)s and their use in preparation of polymer networks

Abstract Novel six-membered bis- and tris-(cyclic carbonate)s that are useful as cross-linking agents in the synthesis of structurally stable yet biodegradable polycarbonates and polyesters have been synthesized in good to moderate yield (85–45%). Cross-linked aliphatic polycarbonates, and polyesters were prepared by copolymerization of the bis-cyclic carbonate (3f) with trimethylene carbonate, and e-caprolactone. The polymers swelled in a wide variety of organic solvents, including CHCl3, CH2Cl2, ethyl acetate, acetone, DMSO, and DMF but not in protic polar solvents, such as methanol, ethanol, and water. Swelling ratios of trimethylene carbonate/3f and e-caprolactone/3f networks at different feed ratios were investigated in dichloromethane. The glass transition temperature of the TMC/3f networks increased with increasing cross-link density.

Diastereo- and enantioselective esterification of butane-2,3-diol catalysed by the lipase from Pseudomonas fluorescens

Abstract Butane-2,3-diol was converted mto the (2R, 3R)-diacetate 5 with 91% de and >98% ee on esterification with vinyl acetate catalysed by the lipase from Pseudomonas fluorescens (Amano P).

Enzyme-catalyzed regioselective transesterification of peracylated sophorolipids

Abstract Regioselective transesterifications and hydrolysis of peracylated sophorolipid (SL) derivatives catalyzed by lipases was investigated. This study is the first evaluation of the lipase-catalyzed reactions on the non-lactonic SL derivatives. Four lipases, namely from porcine pancreas (PPL, Type II), Candida rugosa (AYS, TypeVII), Pseudomonas cepacia (PS-30), and Candida antarctica (Novozym 435, carrier fixed lipase fraction B) were used in anhydrous THF or in phosphate buffer (pH=7.4, 0.2 M). It was confirmed from the detailed spectral analysis of the products that transesterification failed to furnish any free hydroxyls on the sophorose ring. Instead, transesterification took place on the methyl ester located at the carboxylic end of the 17-hydroxyoctadecenoic acid chain attached to the C-1′ position of the sophorose ring. It is proposed that in absence of the lactonic structural motif, the binding of the peracylated non-lactonic SLs in the lipase binding pocket takes place such that the carboxyl group of the octadecenoic acid, not the sophorose sugar, is preferentially accessible to the active site.