A synthesis of (±)-thia-calanolide A, its resolution and in vitro biological evaluation.

A synthesis of (±)-thia-calanolide A 3 has been successfully accomplished starting from 3,5-dimethoxythiophenol 4, in six steps in an overall yield of 4.5%. The key reaction involved Friedel-Crafts tigloylation of 5,7-dihydroxy-4-n-propyl thiocoumarin 6 employing an appropriate solvent of CS2-PhNO2 in a ratio of 7:3. In its biological evaluation for anti-HIV activity, (±)-thia-calanolide A 3 demonstrated comparatively less activity with calanolide A and its synthetic analogue aza-calanolide. Further, (±)-3 has been resolved by chiral HPLC to (+) and (-)-3.

Isolation, characterization and antihyperlipidemic activity of secoisolariciresinol diglucoside in poloxamer-407-induced experimental hyperlipidemia.

CONTEXT: Linum usitatissimum L. (Linaceae), commonly known as flaxseed, is a good source of dietary fiber and lignans. Earlier we reported cardioprotective, antihyperlipidemic, and in vitro antioxidant activity of flax lignan concentrate (FLC) obtained from flaxseed. OBJECTIVES: To isolate secoisolariciresinol diglucoside (SDG) from FLC and to evaluate the antihyperlipidemic activity of SDG in poloxamer-407 (P-407)-induced hyperlipidaemic mice. MATERIAL AND METHODS: FLC was subjected to column chromatography and further subjected to preparative HPTLC to isolate SDG. The chemical structure of the isolated compound was elucidated by UV, IR, (1)H NMR, (13)C NMR, DEPT, COSY, HSQC, HMBC, ROESY, MS, and specific optical rotation was recorded. Further, we have investigated the antihyperlipidaemic effect of SDG (20 mg/kg) in P-407-induced hyperlipidaemic rats. Hyperlipidaemia was induced by intraperitoneal administration of P-407 (30% w/v). Serum lipid parameters such as total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) levels were measured. RESULTS AND DISCUSSION: The structure and stereochemistry of the isolated compound were confirmed on the basis of 1D and 2D spectral data and characterized as SDG. Finally, isolated pure SDG was screened using a P-407-induced mice model for its antihyperlipidemic action using serum lipid parameters. The isolated SDG (20 mg/kg) significantly reduced serum cholesterol, triglyceride (p < 0.001), very low-density lipoprotein (p < 0.05), and non-significantly increased HDL-C. CONCLUSION: Finally, it was concluded unequivocally that SDG showed antihyperlipidaemic effects in P-407-induced hyperlipidaemic mice. Isolated pure SDG confirms that SDG is beneficial in the prevention of experimental hyperlipidemia in laboratory animals.

Enantiomeric separation of novel anticancer agent 5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one.

The enantiomers of 5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one, a novel anticancer agent, were separated by derivatisation with caronaldehyde, separation of the resulting diastereoisomers of the corresponding esters by silica gel column chromatography and regeneration of alcohols (S)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one and (R)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one under aqueous conditions. The absolute configuration of the enantiomers was determined by 1H NMR studies of the corresponding Mosher esters. Alternatively, the enantiomers were separated by preparative HPLC to collect the (S)- and (R)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-ones with high purity which was comparable with that obtained by the chemical method. The details of these methods have been presented herein.

In vitro antiviral activity of bael (Aegle marmelos Corr) upon human coxsackieviruses B1-B6.

The in-vitro antiviral activity of a series of compounds in samples extracted from various parts of the Indian holy tree, Bael (Aegle marmelos corr.) were evaluated for their efficacy against human coxsackieviruses B1-B6. The inhibitory concentrations (IC50) for leaves (L1 and L2) stem and stem bark (S1, S2, S3 and S4) fruit (F1 and F2micro) root and root bark (R1 and R2) and pure compound, the marmelide were 1000 microg/ml (for L1 and L2), 1000 microg/ml (for S1, S2, S3 and S4), 1000 microg/ml (for F1) and 500 microg/ml (for F2) 250 microg/ml (for R1) and 500 microg/ml (for R2) and 62.5 microg/ml for marmelide respectively by plaque inhibition assay at 96 hrs. On the other hand, the corresponding value for Ribavirin, a standard antiviral drug, was 2000 microg/ml for the same viruses at the same time period. These concentrations did not exhibit any toxicity to Vero cells, the host subtoxic concentrations were 5000 microg/ml for leaf and stem fractions 2000 microg/ml for fruit fractions 500 and 1000 microg/ml for root fractions 250 microg/ml for marmelide and 2000 microg/ml for Ribavirin. The cytotoxic concentrations were 8000 microg/ml for leaf and stem compounds 4000 mg/ml for fruit; 1000 microg/ml and 2000 microg/ml for root 500 microg/ml for marmelide and 4000 microg/ml for ribavirin at 96 hrs. These were also confirmed by trypan blue dye exclusion test and further passaging of cells. Additionally pretreatment of host cells, virus inactivation, yield reduction and effect of time of addition assays against coxsackievirus B3 suggested that marmelide was most effective as a virucidal agent besides interfering at early events of its replicative cycle like adsorption, penetration, at various steps in single cycle growth curve and effect of time of addition.