Pharmacological evaluation for anti-asthmatic and anti-inflammatory potential of Woodfordia fruticosa flower extracts.

CONTEXT: Woodfordia fruticosa Kurz. (Lythraceae) flowers are ethnopharmacologically acclaimed in the Indian medicinal system to treat asthma. OBJECTIVE: To evaluate W. fruticosa flower extracts for anti-asthmatic effect. MATERIALS AND METHODS: Ethyl acetate, acetone, methanol, and hydro-alcohol extracts of W. fruticosa flowers were obtained successively and standardized. Ability of extracts to stabilize free radicals and compound-48/80-induced mast cell degranulation was evaluated. In vitro anti-inflammatory potential of extracts at 100 and 200 µg/ml by membrane stabilization and in vivo inhibition of rat paw edema up to 5 h (100 and 200 mg/ml; p.o.) was evaluated. In vitro bronchorelaxant effect was examined against histamine- and acetylcholine (1 µg/ml; independently)-induced guinea pig tracheal contraction. Extracts were evaluated for bronchoprotection (in vivo) ability against 0.1% histamine- and 2% acetylcholine-induced bronchospasm in guinea pigs at 100 and 200 mg/ml; p.o. RESULTS: Standardization studies revealed that the methanol extract exhibited highest polyphenolic (62.66 GAE), and flavonoid (6.32 RE) content and HPLC fingerprinting confirmed the presence of gallic acid (Rt 1.383). IC50 values for DPPH scavenging and metal chelation by the methanol extract were 40.42 and 31.50 µg/ml. Methanol and ethyl acetate extracts at 100 µg/ml exhibited 06.52 and 07.12% of histamine release. Methanol, ethyl acetate, and hydro alcohol extracts at 200 mg/kg demonstrated 32.73, 29.83, 26.75% and 32.46, 9.38, 26.75% inhibition of egg albumin and carrageenan-induced inflammation, respectively. Methanol extract exhibited 100% bronchorelaxation and 48.83% bronchoprotection. CONCLUSION: Woodfordia fruticosa flower (WFF) extracts exhibited anti-asthmatic effect by demonstrating bronchoprotection, bronchorelaxation, anti-inflammatory, antioxidant, and mast cell stabilization ability.

Bronchorelaxant, mast cell stabilizing, anti-inflammatory and antioxidant activity of Randia dumetorum (Retz.) Lamk. extracts.

Randia dumetorum (RD) fruits in different form have been ethnopharmacologically reported to possess antiasthmatic property. Therefore, present study was undertaken to evaluate two different extracts of RD i.e., ethyl acetate (RD-EA) and methanol (RD-ME) for bronchorelaxant, anti-inflammatory, mast cell stabilizing and antioxidant effect along with safety margin, according to OECD guidelines for toxicity. RD-ME and RD-EA (1 mg/mL) exhibited 68.75 and 57.39% inhibition of contraction against acetylcholine, while against histamine induced contraction, inhibition observed was 100 and 78.13%, respectively. Moreover, extracts attenuated the experimentally induced inflammation at 200 mg/kg with % inhibition of 41.62 by RD-ME and 30.36 by RD-EA in carrageenan model, while in egg albumin model RD-ME and RD-EA exhibited % inhibition of 48.31 and 33.75, respectively. In addition, RD-ME and RD-EA at 100 microg/mL demonstrated significant decrease in histamine release of 08.31 and 16.71 in C-48/80 induced mast cell degradation. RD extracts also exhibited antioxidant activity in DPPH, reducing power and metal chelation method, along with safe margin for oral administration as observed in acute toxicity evaluation.

Synthesis, antihypertensive activity, and 3D-QSAR studies of some new p-hydroxybenzohydrazide derivatives.

p-Hydroxybenzohydrazide 2 on treatment with aromatic/aliphatic aldehyde followed by cyclization with carbon disulphide afforded compounds 4a-4n. Also, compound 2 by treatment of substituted isothiocyanate followed by the treatment of chloroacetic acid yields the corresponding compounds 6a-6i. All the test compounds were assayed for antihypertensive activity by non-invasive blood pressure measurement and invasive blood pressure measurement methods. The test compounds showed significant antihypertensive activity. The intact compounds were subjected to 3D-QSAR studies. The 3D-QSAR analysis was carried out by PHASE program and a statistically reliable model with good predictive power (r(2) = 0.98, q(2) = 0.74) was achieved. The 3D-QSAR plots illustrated insights into the structure-activity relationship of these compounds which may aid in the design of potent p-hydroxybenzohydrazide derivatives as antihypertensive agents.

Synthesis of some thiazolyl aminobenzothiazole derivatives as potential antibacterial, antifungal and anthelmintic agents.

A series of 4-(6-substituted-1,3-benzothiazol-2-yl)amino-2-(4-substitutedphenyl)- amino-1,3-thiazoles, 9-24 have been synthesised from 2-chloro-N-(6-substituted-1,3-benzothiazol-2-yl)acetamides, 5-8. The structures of these compounds have been elucidated by spectral (IR, (1)H NMR, Mass) and elemental (C, H, N) analysis data. All the newly synthesised compounds (9-24) were screened for their antibacterial, antifungal and anthelmintic activities. Almost all of these compounds showed moderate to good antimicrobial activity against two gram negative bacteria (E. coli, P. aeruginosa), two gram positive bacteria (S. aureus, B. subtilis), pathogenic fungal strains (C. albicans, A. niger) and good anthelmintic activity against earthworm species (P. corethruses). Compounds 18 and 20 exhibited good antibacterial and antifungal activities, while compound 22 displayed the most significant anthelmintic activity.

Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole.

A series of 6-substituted-[3-substituted-prop-2-eneamido]benzothiazole 9-32 and 6-substituted-2-[(1-acetyl-5-substituted)-2-pyrazolin-3-yl]aminobenzothiazole 33-56 were synthesized using appropriate synthetic route and evaluated experimentally against maximal electroshock test. Selected compounds were evaluated for neurotoxicity, hepatotoxicity and behavioral study. The most active compound, 6-methyl-2-[(1-acetyl-5-(4-chlorophenyl))-2-pyrazolin-3-yl]aminobenzothiazole 52 exhibited an ED50 of 25.49 micromol/kg, TD50 of 123.87 micromol/kg and high protective index (PI) of 4.86 compared to standard drug phenytoin. The 3D-QSAR analysis was carried out by PHASE program and a statistically reliable model with good predictive power (r2=0.9220, q2=0.8144) was achieved. The 3D-QSAR plots illustrated insights into the structure activity relationship of these compounds which may aids in the design of potent aminobenzothiazole derivatives as anticonvulsant agents.

Synthesis and anti-inflammatory activity of alkyl/arylidene-2-aminobenzothiazoles and 1-benzothiazol-2-yl-3-chloro-4-substituted-azetidin-2-ones.

Ten new derivatives of 1-benzothiazol-2-yl-3-chloro-4-substituted-azetidin-2-ones (3a-j) were synthesized using various Schiff bases (alkyl/arylidene-2-aminobenzothiazoles; 2a-j), which in turn were prepared starting from 2-aminobenzothiazole (1). All the synthesised compounds were characterised by elemental analyses and spectral (IR, 1H-NMR, 13C-NMR and EI-MS) data. The title compounds 2a-j and 3a-j were screened in vivo using carrageenan-induced rat paw edema model. All the test compounds showed anti-inflammatory activity when tested in vivo. In general, compounds 3a-j were found to be more potent compared to compounds 2a-j. Among the compounds tested, compound 2g in the alkyl/arylidene-2-aminobenzothiazoles series and compound 3 g in the 1-benzothiazol-2-yl-3-chloro-4-substituted-azetidin-2-ones series were found to be the most potent. All the test compounds were also evaluated to check the gastric ulcer incidence. In gastric ulceration studies, all the test compounds were generally found to be safe at the 100 mg/kg dose level. Furthermore the most potent compounds 2 g and 3 g from each series were screened in vitro for inhibition of both COX-2 and COX-1 catalysed prostaglandin biosynthesis (radiochemical assay). Like most of the commercially available non-steroidal anti-inflammatory drugs (NSAIDs), in the in vitro study, compounds 2 g and 3 g showed anti-inflammatory activity by blocking the metabolism of arachidonic acid to prostaglandin via the cyclooxygenase pathways. In general, in the vitro assay, test compounds 2 g and 3 g were found to be more active after 15 min pre-incubation with the enzyme. Compound 3 g was found to be more COX-2 selective, while compound 2 g was found to be equally COX-2 and COX-1 selective.

Synthesis and anticonvulsant activity of 3-(6-substituted-benzothiazol-2-yl)-6-phenyl-[1, 3]-xazinane-2-thiones.

A new series of 3-(6-substituted-benzothiazol-2-yl)-6-phenyl-[1, 3]-oxazinane-2-thiones (4a-j) has been synthesised using an appropriate synthetic route (Scheme 1) and characterised by elemental analyses and spectral (IR, (1)HNMR, (13)C NMR, and EI MS) data. The anticonvulsant activity of all the title compounds (4a-j) was evaluated against Maximal Electroshock (MES) induced seizures and furthermore the most potent compounds were evaluated against subcutaneous pentylenetetrazole (sc PTZ) induced seizures model in mice. The neurotoxicity was assessed using the rotorod procedure. All the test compounds were administered intraperitoneally at various dose levels ranging from 30-200 mg/kg body wt and the median effective dose (ED(50)), median toxic dose (TD(50)), and protection index (PI) values were determined (Table 2). Among the compounds tested, the 3-(6-dimethylaminobenzothiazol-2-yl)-6-phenyl-[1, 3]-oxazinane-2-thiones (4j) was found to be the most potent (ED(50): 9.85 and 14.8 in MES model and 12 and 17 in scPTZ model at t = 0.5 h and 4 h, respectively, and TD(50) 42.8 and 44 at t = 0.5 h and 4 h, respectively, which has been found to be significant at p < 0.01 with respect to reference standard phenytoin) with protection index (PI) 4.85.