Partial syntheses of aromatic amides: their anti-urease potential and docking studies.

The aromatic amide: N-p-trans-coumaroyltyramine (1) was isolated for the first time from the stem bark of Celtis zenkeri (Ulmaceae). Its four new derivatives (1a-d) and previously reported diacetylated product (1e) have been synthesized and characterized spectroscopically followed by their in vitro screening for anti-urease potential. The diacetylated product (1e) was found to be the most potent inhibitor with an IC50 value of 19.5 ± 0.23 µM compared to thiourea used as standard (21.5 ± 0.47 µM). Furthermore, molecular docking studies were conducted revealing striking interactions of the active compounds with catalytically important residues such as His593, Ala636 and Asp633. Subsequently, the prime MM-GBSA calculations provided the ligand binding and strain energies. The molecular dynamic simulations validated the docked and post-docked complexes where compounds 1b, 1c, 1d and 1e remained stable throughout the simulation. This study provides insight into the N-p-trans-coumaroyltyramine derivatives (1b-e) that can block the substrate entry, thereby inhibiting the urease's catalytic activity. Hence, these hit compounds can proceed for further pre-clinical studies for drug discovery against urease.Communicated by Ramaswamy H. Sarma.

Antiulcerogenic effects and possible mechanism of action of Quassia amara (L. Simaroubaceae) extract and its bioactive principles in rats.

The effects of Quassia amara extract (Q. amara) and its bioactive principles-quassin and 2-methoxycanthin-6-one on gastric ulceration were studied in albino rats. Q. amara (200-800 mg/kg p.o.; 5-20 mg/kg i.p) and 2-methoxycanthin-6-one (12.5, 25.0 and 50.0 mg/kg p.o; 1, 2 and 4 mg/kg i.p) but not quassin (12.5, 25.0 and 50 mg/kg p.o; 1, 2 and 4 mg/kg i.p) significantly inhibited gastric ulceration induced by indomethacin (40mg/kg). Administration of Q. amara (800 mg/kg p.o and 20 mg/kg i.p) and 2-methoxycanthin-6-one (12.5 mg/kg p.o; 4 mg/kg i.p) caused between 77%-85% cytoprotection against indomethacin (40 mg/kg, i.p) - induced gastric ulceration. Quassin did not cause any significant change in indomethacin-induced gastric ulceration. The inhibition of gastric ulceration produced by Q. amara and 2-methoxycanthin-6 one was accompanied by significant dose-dependent decreases (P< 0.01) in total gastric acidity. To investigate the probable mechanism of action, the individual effects of the extract and its principles alone and in combination with histamine (1 mg/kg) or cimetidine (0.12 mg/kg) on gastric acid secretion in situ were studied. Q. amara (20 mg/kg) and 2-methoxycanthin-6-one (4 mg/kg) but not quassin significantly (P< 0.01) inhibited the basal and histamine-induced gastric acid secretion. Inhibition of gastric acid secretion by Q. amara and 2-methoxycanthin-6-one was accentuated by cimetidine. The results suggest that Q. amara and its bioactive principle, 2-methoxycanthin-6-one possess antiulcer activity probably acting via histamine H2 receptor. This could be a potential source of potent and effective antiulcer agents.

Chemical composition, toxicity and antioxidant activities of essential oils of stem bark of Nigerian species of guava (Psidium guajava Linn.).

Essential oil from the stem bark of Nigerian species of Psidiumguajava of the family Myrtaceae was obtained by hydro-distillation using an all-glass Clavenger apparatus. GC and GC/MS analysis were carried out on the essential oil and was found to contain 62 compounds constituting 99.98 % of the total oil composition. The principal constituents are hydrocarbons, amines, amides and esters with 3,6-dioxa-2,4,5,7-tetraoctane,2,2,4,4,5,5,7,7-octamethyl (11.67 %) and cyclononane (10.66 %) dominating the total essential oil. Brine shrimp lethality test was carried out to determine the toxicity of the oils to living organisms (shrimps). LC50 value (µg/ml) of 1.0009 obtained showed that the essential oil of P. guajava stem bark was toxic. The antioxidant property of essential oil was investigated by measuring the decrease in absorption at 517 nm of 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) in a UV/visible spectrophotometer. The oil showed better activity as a radical scavenger than α-tocopherol. The oil activity was 71.83 % at 0.2 mg/ml and the absorption is stoichiometric with respect to the number of electron taken up. Thus, the results of this study showed that the essential oil from P.guajava was not only toxic; it possessed antioxidant activity, which could exert beneficial actions against pathological alterations caused by the presence of highly reactive free radicals. The toxicity of the oil can be taken advantage of in the therapy of diseases involving cell or tumor growth.