Sanjay Malhotra

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.

Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part I: Dioxygenated 4-methyl coumarins as superb antioxidant and radical scavenging agents.

Twenty-three 4-methylcoumarins bearing different functionalities have been examined for the first time for their effect on NADPH-catalysed liver-microsomal lipid peroxidation with a view to establish structure-activity relationship. Dihydroxy- and diacetoxy-4-methylcoumarins produced dramatic inhibition of lipid peroxidation. 7,8-Diacetoxy-4-methylcoumarin and 7,8-dihydroxy-4-methylcoumarin were found to possess superb antioxidant and radical scavenging activities.

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.

Hydrolytic reactions on polyphenolic perpropanoates by porcine pancreatic lipase immobilized in microemulsion-based gels

Abstract Porcine pancreatic lipase (PPL) has been immobilized in microemulsion-based gels (MBGs). Highly selective and efficient deacylation of di/trihydric phenolic perpropanoates has been observed on incubating them with immobilized PPL. These reactions can find general utility in Synthetic Organic Chemistry.

Determination of Excited Singlet-State Dipole Moments of Methoxy and Dimethylamino Substituted Benzylidenebenzosuberones Using Solvatochromic Method

The solvent effects on the electronic absorption and emission fluorescence spectra for a series of chalcone cyclic analogues were studied. The singlet-state excited dipole moments and the ground state dipole moments of the cyclic chalcone analogues E-2- benzylidene-1-benzosuberone E-2-(4′-methoxybenzylidene)-1-benzosuberone E-2-(4′-dimethylaminobenzylidene)-1-benzosuberone were calculated by using solvatochromic shift method by means of equations using the variations of Stokes’ shift with the solvents dielectric constant and refractive index values. It was found that the excited state dipole moments calculated by the solvatochromic shift method were greater than the ground state dipole moments indicating a substantial redistribution of the pi-electron densities in a more polar excited state for each derivative.

[1-(4-Chlorophenyl)-3-(4-methoxyphenyl)-pyrazol-5-yl]acetonitrile

The title compound, C18H14ClN3O, was obtained as one of the products from the condensation of 4-chlorophenylhydrazine hydrochloride with 6-(4-methoxyphenyl)-4-methylthio-2-oxo-2H-pyran-3-carbonitrile. The best planes through the phenyl rings in the methoxyphenyl and chlorophenyl groups are aligned at angles of 7.02 (8) and 56.19 (4)°, respectively, relative to the pyrazole ring.

6-Acetyl-3,4-dihydro-2,2-dimethyl-2H-benzopyran-3,7-diyl Diacetate

The title compound, C17H20O6, is an important precursor in the synthesis of a biologically active chalcone. It contains the dihydropyran unit in a distorted chair conformation, with the 3-acetoxy group arranged in an axial position.

3-Cyano-6-(2-methoxyphenyl)-4-methylthio-2H-pyran-2-one

The molecule of the title compound, C 14 H 11 NO 3 S, is approximately planar with the two six-membered rings inclined at an angle of 10.99 (12)°.

3-[3-(4-Bromophenyl)-1-phenylpyrazol-5-yl]-2H-1-benzopyran-2-one

In the title compound, C 24 H 15 BrN 2 O 2 , the angles formed by the planes of the bromophenyl, phenyl and coumarin groups with the plane of the pyrazole nucleus are 19.3, 38.8 and 65.6°, respectively. The absolute structure has been determined.