Nawal K. Sharma

Polyphenols and alkaloids from piper species

Abstract Thirty eight compounds of different types have been isolated from twelve Piper species. The ether extract of the leaves of P. aduncum yielded eleven compounds, out of which 2,6-dimethoxy-4-(2-propenyl)phenol was isolated for the first time from the genus Piper and 2-acetoxy-1,3-dimethoxy-5-(2-propenyl)benzene is a new compound. The petrol extract of the stems and leaves of P. attenuatum furnished a novel long chain alcohol, 14-benzo 1 , 3 dioxol-5-yl-tetradecan-2-ol. From P. betle, β-sitosteryl palmitate was isolated for the first time from the genus Piper. A novel amide, 3-(3,4-dimethoxyphenyl)propanoyl pyrrole has been obtained from P. brachystachyum. Nerolidol was isolated for the first time from P. falconeri. From the methanol extract of the stems and leaves of P. khasiana, piperlonguminine, piperine, apigenin dimethyl ether and β-sitosterol were obtained. Retrofractamide A was obtained for the first time from P. longum; the structure of (+)-asarinin, isolated from P. longum, was confirmed by X-ray crystallographic studies. Retrofractamide A, apigenin dimethyl ether, tetratriacontanol and tectochrysin were isolated from P. manii. P. pedicellosum furnished β-sitosterol, pellitorine, piperlonguminine, cepharadione A and furacridone, the last compound being isolated for the first time from the genus Piper.

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.

Synthesis, Characterization and In Vitro Anti-invasive Activity Screening of Polyphenolic and Heterocyclic Compounds

Invasion is the hallmark of malignant tumors, and is responsible for the bad prognosis of the untreated cancer patients. The search for anti-invasive treatments led us to screen compounds of different classes for their effect in an assay for invasion. Thirty-nine new compounds synthesized in the present study along with 56 already reported compounds belonging mainly to the classes of lactones, pyrazoles, isoxazoles, coumarins, desoxybenzoins, aromatic ketones, chalcones, chromans, isoflavanones have been tested against organotypic confronting cultures of invasive human MCF-7/6 mammary carcinoma cells with embryonic chick heart fragments in vitro. Three of them (a pyrazole derivative, an isoxazolylcoumarin and a prenylated desoxybenzoin) inhibited invasion at concentrations as low as 1 microM; instead of occupying and replacing the heart tissue within 8 days, the MCF-7/6 cells grew around the heart fragments and left it intact, when treated with these compounds. At the anti-invasive concentration of 1 microM, the three compounds did not affect the growth of the MCF-7/6 cells, as shown in the sulforhodamine B assay. Aggregate formation on agar was not stimulated by any of the three anti-invasive compounds, making an effect on the E-cadherin/catenin complex improbable. This is an invasion suppressor that can be activated in MCF-7/6 cells by a number of other molecules. Our data indicate that some polyphenolic and heterocyclic compounds are anti-invasive without being cytotoxic for the cancer cells.

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.

Regioselective deacylation of polyacetoxy aryl-methyl ketones by lipases in organic solvents☆

Abstract Lipases from porcine pancreas and Candida cylindraea, suspended in organic solvents have been used to study regioselective deacylation of polyacetoxy acetophenones. It has been observed that the hydrolysis of acetate groups at positions other than ortho predominates.

An aristolactam from Piper acutisleginum and revision of the structures of piperolactam B and D

Abstract A new aristolactam, 10-amino-4-hydroxy-2,3-dimethoxyphenanthrene-1-carboxylic acid lactam, was isolated from the stem of Piper acutisleginum . The structures of two related alkaloids, piperolactam B and D, have been revised.

Regioselective enzyme-catalyzed deacetylation of benzyl phenyl ketone peracetates in organic solvents☆

Abstract Lipases from porcine pancreas and Candida cylindracea, suspended in different organic solvents have been used to deacetylate peracetates of benzyl phenyl ketones (desoxybenzoins). High regioselectivity in the reactions has been observed, also the nature of the solvent affects the rate of the reaction.

Biotransformations in the regioselective deacetylation of polyphenolic peracetates in organic solvents

Regioselectivity has been observed in the deacetylation of peracetates of polyphenolic aromatic ketones by lipases from porcine pancreas (PPL) and Candida cyclindracea (CCL) suspended in organic solvents. The deacetylation of acetoxyl groups at positions para and meta to the carbonyl (ketonic) group is favoured over the one at the ortho position.

Potential applications of enzyme-mediated transesterifications in the synthesis of bioactive compounds

The yeast lipase Candida cylindracea (CCL) and porcine pancreatic lipase (PPL) have been used for regioselective deacylation of peracetylated benzopyrones, diphenylpropenones and acetophenones for the first time. The deacylation study on different classes of polyphenols has revealed that the presence of carbonyl group attached to the aromatic ring is needed by the lipases to exhibit regioselectivity towards hydrolysis of acetoxyl groups. The acetoxyl groups at positions other than the one at ortho position to the carbonyl group get selectively hydrolysed by PPL in orgnnic solvents. The trnnsesterification reactions using triflouroethylbutyrate (TFEB), catalysed by PPL and CCL on some polyols in dry organic solvents were also performed. It was found that the primary hydroxyl is acylated. In D-panthenol, the oxidised dextrorotatory form of which is a major constituent of vitamin B-complex, the primary hydroxyl group at the far end of the asymmetric carbon atom gets exclusively acylated. This work should be of importance in the synthesis of building blocks of biologically active natural products which may provide structural leads to anti AIDS and anticancer agents.

A wax ester from Piper clarkii

Abstract A novel type of wax ester has been isolated from a petrol extract of stems and leaves of Piper clarkii and its structure established as 3-(4-hydroxyphenyl)propyl tetracosanoate. The structure was verified by synthesis. The oxygenated cyclohexane (+)-crotepoxide and β-sitosterol were also isolated.