Farzana Shaheen

Anticonvulsant activities of ethanolic extract and aqueous fraction isolated from Delphinium denudatum

Dried roots of Delphinium denudatum Wall. are a popular folk remedy for the treatment of epilepsy in the traditional Unani system of medicine in the sub-continent. We carried out anticonvulsant screening of the ethanolic extract (EE) and aqueous fraction (AF) of this plant utilising the maximal electroshock (MEST) and subcutaneous pentylenetetrazole (scPTZ), bicuculline (scBIC), picrotoxin (scPTX) and strychnine (scSTN) tests for anticonvulsant activity. EE had weak dose-dependent anticonvulsant effects on seizures induced by PTZ and BIC. AF exhibited dose-dependent activity against hind limb tonic extension phase (HLTE) of MEST and comparatively stronger anticonvulsant activity against seizures induced by PTZ and BIC. The results suggest the presence of potent anticonvulsant compounds in AF of D. denudatum and deserve further investigation for isolation of active compounds and elucidation of the mechanism of anticonvulsant action.

Biotransformation of (+)-androst-4-ene-3,17-dione

Fermentation of (+)-androst-4-ene-3,17-dione (1) with Curvularia lunata for 10 days yielded five oxidative and reductive metabolites, androsta-1,4-diene-3,17-dione (2), 17β-hydroxyandrosta-1,4-dien-3-one (3), 11α-hydroxyandrost-4-ene-3,17-dione (4), 11α,17β-dihydroxyandrost-4-en-3-one (5) and 15α-hydroxyandrosta-1,4-dien-17-one (6). The structures of these metabolites were elucidated on the basis of spectroscopic techniques. These microbially transformed products were assayed against the clinically important enzymes, tyrosinase and prolyl endopeptidase.

Microbial transformation of (+)-androsta-1 ,4-diene-3,17-dione by Cephalosporium aphidicola.

Fermentation of (+)-androsta-1,4-diene-3,17-dione ( 1 ) with Cephalosporium aphidicola for 8 days yielded oxidative and reductive metabolites, androst-4-ene-3,17-dione ( 2 ), 17 g -hydroxyandrosta-1,4-diene-3-one ( 3 ), 11 f -hydroxyandrosta-1,4-diene-3,17-dione ( 4 ), 11 f -hydroxyandrost-4-ene-3,17-dione ( 5 ), 11 f ,17 g -dihydroxyandrost-4-ene-3-one ( 6 ) and 11 f ,17 g -dihydroxyandrosta-1,4-diene-3-one ( 7 ). The fermentation of 1 with Fusarium lini also yielded metabolites 3-7 . The structures of these metabolites were elucidated on the basis of spectroscopic techniques.

Norditerpenoid alkaloids from the roots of Aconitum heterophyllum Wall with antibacterial activity

Two new aconitine-type norditerpenoid alkaloids 6-dehydroacetylsepaconitine (1) and 13-hydroxylappaconitine (2), along with three known norditerpenoid alkaloids lycoctonine, delphatine and lappaconitine were isolated from the roots of the Aconitum heterophyllum Wall. These compounds exhibited significant antibacterial activity. The structure of compound 1 and 2 were deduced on the basis of their spectral data.

New inhibitors of ROS generation and T-cell proliferation from Myrtus communis.

Phytochemical investigation on Myrtus communis Linn. afforded myrtucommuacetalone (1) with an unprecedented carbon skeleton and a new phloroglucinol-type compound, myrtucommulone M (2), along with four known constituents 3-6. Their structures were established by extensive analyses of NMR and mass spectral data as well as by single-crystal X-ray diffraction studies. These constituents were evaluated for their ability to modulate the immune response, based on their effects on various components of immune system. Compounds 1 and 5 exhibited significant inhibitory effect against nitric oxide (NO(•)) production. Compound 1 also exhibited significant antiproliferative activity (IC50 < 0.5 μg/mL) against T-cell proliferation. Myricetin (3) exerted a significant inhibition (IC50 = 1.6 μg/mL) on zymosan-stimulated whole blood phagocytes ROS production. Compounds 1 and 3 were active against PMA-stimulated ROS generation.

New diterpenoid alkaloids from Aconitum heterophyllum Wall: Selective butyrylcholinestrase inhibitors.

Two new diterpenoid alkaloids, heterophyllinine-A (1) and heterophyllinine-B (2), along with two known alkaloids dihydroatisine (3) and lycoctonine (4) were isolated from the roots of Aconitum heterophyllum Wall. The structure of (1) and (2), were deduced on the basis of spectral data. Compounds 1–2 inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent manner with percent inhibition ranging between 4.24% and 6.94 % and 79.1 % and 82.75 % for AChE and BChE, respectively indicating that compounds 1 and 2 are about thirteen times more specific to BChE than AChE.

Microbial transformation of cortisol and prolyl endopeptidase inhibitory activity of its transformed products

Incubation of cortisol (1) with Gibberella fujikuruoi for 12 days yielded an oxidatively cleaved product, 11β-hydroxyandrost-4-en-3,17-dione (2), while incubation with Bacillus subtilis and Rhizopus stolonifer yielded the reduced product, 11β, 17α,20,21-tetrahydroxy-(20S)-pregn-4-en-3-one (3). Other reduced products, 11β, 17α, 21-trihydroxy-5α-pregnan-3, 20-dione (4) and 3β, 11β, 17α, 21-tetrahydroxy-5α-pregnan-20-one (5) were obtained by incubation of compound 1 with Bacillus cerus. The inhibitory activity of compounds 1-5 against prolyl endopeptidase enzyme (PEP) was also assayed. Compounds 2 (IC50 162.8 μM) and 4 (IC50 157 μM) have shown significant inhibitory activity against PEP.

Solid-phase total synthesis of cyclic decapeptide phakellistatin 12.

Pakellistatin 12 (1) is a new cancer cell growth inhibitory (P388 ED 50 2.8 microg/mL) cyclodecapeptide that was isolated from a marine sponge Phakellia sp. The first total synthesis of compound 1 is reported here using solid-phase methodology with safety-catch linker strategy. For the sequence of amino acids in the cycle, the peptide product was analyzed with a MALDI TOF/TOF instrument, and the structure of the synthetic product was found to be chemically and spectroscopically identical to the natural substance.

Antioxidant flavonoids from Tamus communis ssp. cretica

A new flavonoid, kaempferol-3,4′-di-O-α-L-rhamnopyranoside (1), and three known flavonoids (2–4) were isolated from the aerial parts of T. communis L. The structure of the new compound was elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed significant antioxidant activity (IC50 187.151 ± 0.821 μM, and 92.079±0.513 μM, respectively), whereas compounds 3 and 4 showed moderate activity in DPPH free radical scavenging assays.

In vitro inhibition of pentylenetetrazole and bicuculline-induced epileptiform activity in rat hippocampal pyramidal neurons by aqueous fraction isolated from Delphinium denudatum.

Roots of Delphinium denudatum W. are used for the treatment of epilepsy by traditional healers in subcontinent. Aqueous fraction (AF) isolated from D. denudatum has previously shown significant anticonvulsant activity in in vivo and in vitro models of seizures. We investigated anticonvulsant effects of AF on pentylenetetrazole (PTZ) and bicuculline (BIC)-induced epileptiform activity in primary hippocampal neuronal cultures. Electrophysiological studies on single pyramidal neurons were carried out by using whole-cell current clamp technique. Introduction of AF (0.6 mg/ml) in perfusate blocked PTZ (10 mM) and BIC (100 micro M)-induced epileptiform activity comprising of paroxysmal depolarization shifts (PDS). The PDS were elicited again when AF was removed from perfusate. We conclude that AF contains anticonvulsant compounds that possibly interact with GABA(A) receptor to produce blockade of epileptiform activity. Further studies on isolation of compounds from AF may lead to discovery of new class of anticonvulsants.