Pharmacophore modeling, design, and synthesis of potent antihypertensives, oxazolo/thiazolo-[3,2-a]-pyrimidin-3(2H)-one, and 1,5-dihydroimidazo-[1,2-a]-pyrimidin-3(2H)-one derivatives: A pilot trial.

An improved pharmacophore model, molecular properties, geometric analyses, and SAR led to synthesize oxazolo/thiazolo-[3,2-a]-pyrimidin-3(2H)-one, and 1,5-dihydroimidazo-[1,2-a]-pyrimidin-3(2H)-one derivatives exhibiting potent anti-hypertensive activity. The 6-ethoxycarbonyl-2,7-dimethyl-5-phenyl-1,5-dihydroimidazo[3,2-a]pyrimidin-3(2H)-one (4g), and 6-ethoxycarbonyl-2,7-dimethyl-5-(3-methyl-phenyl)-1,5-dihydroimidazo[3,2-a]pyrimidin-3(2H)-one (4h) showed significant reduction in mean arterial blood pressure (MABP, mm/Hg) of 79.78%, and 92.95% in 6 and 12 h durations, respectively, at 1.5 mg/kg body-weight dose, while at 3.0 mg/kg body-weight dose, the MABP reduction was achieved at 95.46%, and 92.02%, respectively, in 6 and 12 h durations, as compared to the standard drug, nifedipine.

Novel glycoside from Wedelia calendulacea inhibits diethyl nitrosamine-induced renal cancer via downregulating the COX-2 and PEG2 through nuclear factor-κB pathway.

A new compound derivative of glycoside 19-α-hydroxy-ursolic acid glucoside (19-α-hydroxyurs-12(13)-ene-28-oic acid-3-O-ß-D-glucopyranoside (HEG) was isolated from whole plant of Wedelia calendulacea (Compositae). The structure was elucidated and established by standard spectroscopy approaches. Diethylnitrosamine (DEN) (200 mg/kg) and ferric nitrilotriacetate (Fe-NTA) (9 mg/kg) were used for induction of renal cell carcinoma (RCC) in the rats. The rats were further divided into different groups and were treated with HEG doses for 22 weeks. Anti-cancer effect in RCC by HEG was dose dependent to restrict the macroscopical changes as compared to DEN + Fe-NTA-control animals. Significant alteration in biochemical parameters and dose-dependent alleviation in Phase I and Phase II antioxidant enzymes were responsible for its chemo-protective nature. HEG in dose-dependent manner was significant to alter the elevated levels of pro-inflammatory cytokines and inflammatory mediators during RCC. The histopathological changes were observed in the HEG pre-treated group, which was proof for its safety concern as far as its toxicity is concerned. The isolated compound HEG can impart momentous chemo-protection against experimental RCC by suppressing the cyclooxygenase (COX-2) and prostaglandin E2 (PGE2) expression via nuclear factor-kappa B (NF-κB) pathway.

An interactive human carbonic anhydrase-II (hCA-II) receptor--pharmacophore molecular model & anti-convulsant activity of the designed and synthesized 5-amino-1,3,4-thiadiazole-2-thiol conjugated imine derivatives.

New imines, derived from aromatic aldehyde, chalcones and 5-amino-1,3,4-thiadiazole-2-thiol exhibited promising anti-convulsant activity which is explained through chemo-biological interactions at receptor site producing the inhibition of human Carbonic Anhydrase-II enzyme (hCA-II) through the proposed pharmacophore model at molecular levels as basis for pharmacological activity. The compounds 5-{1-(4-Chlorophenyl)-3-[4-(methoxy-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2b), 5-{[1-(4-chloro-phenyl)]-3-[4-(dimethyl-amino-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2c) and 5-{[1-(4-chloro-phenyl)]-3-[(4-amino-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2f) showed 100% activity in comparison with standard Acetazolamide, a known anti-convulsant drug. The compounds 2c, 2f also passed the Rotarod and Ethanol Potentiation tests which further confirmed them to be safe in motor coordination activity and safe from generating neurological toxicity.

Osteosaponins 1 and 2: two new saponin glycosides from Osteospermum vaillantii.

Osteospermum vaillantii (Decne) T. Norl., collected from southern Saudi Arabia, yielded two new saponins characterised as 3-O-beta-D-glucopyranosyl-(2' --> 1'')-beta-D-glucopyranosyl-(3' --> 1''')-O-beta-D-galactopyranosyl-oleanolic acid, designated as osteosaponin, and 3-O-beta-D-glucopyranosyl-(2' --> 1'')-beta-D-glucopyranosyl-(2''-1''''')-beta-D-glucopyranosyl-(3' --> 1''')-O-beta-(-D-galactopyranosyl-oleanolic-acid-28-C(O)-O-beta-D-(1'''')-glucopyranosyl ester, designated as osteosaponin. The sugar attachments and configurations were confirmed by spectroscopic methods, that is, 1H, 13C-NMR, COSY, HSQC and HMBC-NMR experiments.

Syntheses and anti-depressant activity of 5-amino-1, 3, 4-thiadiazole-2-thiol imines and thiobenzyl derivatives.

A number of new imine derivatives of 5-amino-1, 3, 4-thiadiazole-2-thiol have been synthesized, and their anti-depressant activity was tested using imipramine as reference drug. Two compounds namely 5-{[1-(4-chlorophenyl)-3-(4-methoxy-phenyl)prop-2-en-1-ylidene]-amino}-5-benzylthio-1, 3,4 -thiadiazole 4i(b) and 5-{[1-(4-chlorophenyl)-3-(4-dimethyl-aminophenyl)-prop-2-en-1-ylidene]amino}-5-benzylthio-1,3,4-thiadiazole 4i(c) have shown significant anti-depressant activity, which decreased immobility time by 77.99% and 76.26% compared to the standard imipramine (82%). All the compounds in the series have passed neurotoxicity tests.

Three new diterpenes and the biological activity of different extracts of Jasonia montana.

Three new diterpenes, namely jasonin-a (1), jasonin-b (2), and jasonin-c (3) were isolated from the aerial parts of Jasonia montana (Asteraceae). Their structures were elucidated on the basis of spectral data as [(1E)-2-((2S)-1,2,5-trimethylbicyclo[3.2.l]octan-8-yl)vinyl] benzene-3-carboxylic acid (1), [3-((2S, 5S)-1,2, 5-trimethylcycloheptanyl)propyl]benzene-3-carboxylic acid (2), and [(1E)-3-((7R)-1,7-dimethy-4-methylenecycloheptanyl)prop-1-enyl] benzene-3-carboxylic acid (3). In addition, the previously reported 5,7,3'-trihydroxy-3,6,4'-trimethoxy flavone designated as centaureidin (4), was also isolated and characterized from this source. The different extracts of the plant were also screened for hypoglycemic, antidiabetic, and antimicrobial activities, wherein the petroleum ether and ethanolic extracts exhibited hypoglycemic and antidiabetic activity, and the petroleum ether and chloroform extracts showed antimicrobial activity.

Three new and two rare furanoeremophilanes from Senecio asirensis.

Three new furanoeremophilanes have been obtained from the aerial parts of Senecio asirensis (N. O. Asteraceae), and characterized as 6-hydroxylmethyl-9-methoxyl-4,11-dimethylnaphtho[2,3-b]furan, designated asirensane-a (1), 6-hydroxyl-1,2-dimethoxyl-4,6,11-trimethyl-6-hydronaphtho[2,3-a]furan-7-one, named asirensane-b (2), and (6,12-dihydroxyl-9-methoxyl-4-methyl-11-acetyl-3,4-dihydronaphtho[2,3-b]furan- 3-yl)methyl (2'Z)-2'-methyl-but-2'-enoate, designated asirensane-c (3). In addition, two rare furanoeremophilanes have also been isolated and characterized from this source, namely 9-methoxyl-4,11-dimethylnaphtho[2,3-b]furan, named 14-nordehydro-calohastine (4), and 4,11-dimethylnaphtho[2,3-b]furan-6,9-dione, designated as maturinone (5). Their structures have been elucidated on the basis of spectral analysis. The alcoholic extract was also tested for anti-inflammatory activity, which decreased edema by 22% at a dose of 500 mg kg-1 after 3 h with respect to the control group treated only with carrageenan, while the standard drug phenylbutazone showed a 50% decrease at a dose of 100 mg kg-1, indicating that the extract has moderate anti-inflammatory activity.

Verbenacine and salvinine: two new diterpenes from Salvia verbenaca.

Two new diterpenes namely verbenacine (1) and salvinine (2) have been isolated from the aerial parts of Salvia verbenaca. Their structures have been elucidated on the basis of chemical and spectral data as 3alpha-hydroxy-19-carboxykaur-15-ene and 19-hydroxy-12,14-dioxo labda-15,17-diene.

Antihepatotoxic activity of seeds of Cichorium intybus.

The different fractions of alcoholic extract and one phenolic compound AB-IV of seeds of Cichorium intybus Linn were screened for antihepatotoxic activity on carbon tetrachloride (CCl(4))-induced liver damage in albino rats. The degree of protection was measured using biochemical parameters like aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALKP), and total protein (TP). The methanol fraction and compound AB-IV were found to possess a potent antihepatotoxic activity comparable to the standard drug Silymarin (Silybon-70). The histopathological study of the liver was also carried out, wherein the methanolic fraction and compound AB-IV showed almost complete normalization of the tissues as neither fatty accumulation nor necrosis was observed.

Scropolioside-D2 and harpagoside-B: two new iridoid glycosides from Scrophularia deserti and their antidiabetic and antiinflammatory activity.

Five iridoid glycosides, including the two new compounds scropolioside-D(2) (1) and harpagoside-B (2), were isolated from the aerial parts of Scrophularia deserti DEL (Scrophulariaceae). Their structures were elucidated on the basis of spectral data to be 6-O-[2",4"-di-O-acetyl-3"-O-trans-cinnamoyl)-alpha-L-rhamnopyranosyl]-8 alpha-hydroxymethyl-1 alpha,5 beta,6 alpha,7 alpha,9 beta-pentahydro-7(8)-epoxy-2-oxaind-3-ene-1-O-beta-D-glucopyranoside-6'-O-acetate (1) and 5-O-beta-hydroxy-8-O-beta-trans-cinnamoyl-8 alpha-methyl-1,6,7,9-tetrahydro-2-oxaind-3-ene-1-O-beta-D-glucopyranoside (2), respectively. In addition, three more iridoid glycosides, scropolioside-D (3), koelzioside (4), and 8-O-acetyl-harpagide (5), were also isolated and characterized from this source. The biological activity and the structure activity relationship of the compounds were also studied, and scropolioside-D (3) and harpagoside-B (2) were found to possess significant antidiabetic and antiinflammatory activity, respectively.

Verticillarone: a new seco-fusicoccane diterpenoid ketonepoxide from Hypoestes verticillaris.

The aerial parts of Hypoestes verticillaris (L.F.) Sol. (Acanthaceae) has afforded a new seco-fusicoccane diterpenoid ketonepoxide, which was characterized as 1(10) seco-fusicocc-3 (4)-ene-5, 11, 14-trione-8 (9), 1 (7)-diepoxide (1) on the basis of spectral analysis and named as verticillarone, along with earlier reported diterpenoid, i.e. 13-hydroxy-7-oxo-labda-8, 14-diene (2).

Hepatoprotective activity of two plants belonging to the Apiaceae and the Euphorbiaceae family.

The different extracts of Apium graveolens Linn. (Apiaceae) and Croton oblongifolius Roxb. (Euphorbiaceae) were tested for their hepatoprotective activity against CCl(4) induced hepatotoxicity in albino rats. The degree of protection was measured by using biochemical parameters like serum transaminases (SGOT and SGPT), alkaline phosphatase, total protein and albumin. The methanolic extracts showed the most significant hepatoprotective activity comparable with standard drug silymarin. Other extracts namely petroleum ether and acetone also exhibited a potent activity.