Gastric Antisecretory and Anti-ulcer Effect of ME3407, a New Benzimidazole Derivative, in Rats

Abstract

The effects of a new benzimidazole derivative, ME3407 (n-butyl-2-(thiazolo-[5,4-b]pyrid-2-yl) sulfinylacetate, CAS 133903-90-9), on gastric acid secretion and gastric and duodenal ulcers in rats were examined. ME3407, given orally, inhibited dose-dependently (0.3-30 mg/kg) the incidence of gastric lesions such as Shay ulcers, and water-immersion stress-, acetylsalicylic acid (ASA)- and histamine-induced erosions. In addition, ME3407 showed marked therapeutic effect on HCl- and ASA-induced lesions. In the lumen-perfused rats, oral administration of ME3407 inhibited dose-dependently (1-100 mg/kg) gastric acid secretion induced by histamine and tetragastrin with ED50 values of 3.02 and 3.37 mg/kg, respectively. Oral administration of ME3407 at a dose of 30 mg/kg also inhibited the elevation of serum gastrin level. The development of duodenal ulcers caused by mepirizole and systeamine was also potently inhibited by ME3407 at an oral dose of 0.1-30 mg/kg. However, when given at 30 mg/kg intraduodenally, subcutaneously or intravenously, ME3407 did not inhibit these acutely induced gastric elosion and acid output. ME3407 was not detected in the serum upon oral administration. These results indicated that ME3407 was active only by oral administration, and exerts direct action on the ulcers and acid secretion from the gastric membrane.

Benzimidazole derivatives: A versatile scaffold for drug development against Helicobacter pylori‐related diseases

“…62 In recent years, many investigators have focused on developing multi-targeting short-acting therapeutics agents with durable effects to treat acid-induced and H. pylori-induced ulcers. 63,64 The anti-ulcerative activities of benzimidazole derivatives have been reviewed by Patil et al; however, we here discussed two additional studies that had not been addressed by the recent review. 13 Noor et al assessed the anti-ulcerogenic activity of benzimidazole-pyrazole hybrid molecules in ethanolinduced gastric ulcer rat models.…”

“…Also, ME3407 exhibited greater antisecretory effects than omeprazole (as a PPI) and famotidine (as a H 2 receptor antagonist) in different in vivo models. 64…”

“…Peptic ulcer is divided into two distinct groups; stomach ulcers (i.e., gastric ulcers [GU]) and duodenal ulcers (DU), which are the most common H. pylori ‐related complications, especially in developing countries 62 . In recent years, many investigators have focused on developing multi‐targeting short‐acting therapeutics agents with durable effects to treat acid‐induced and H. pylori ‐induced ulcers 63,64 . The anti‐ulcerative activities of benzimidazole derivatives have been reviewed by Patil et al; however, we here discussed two additional studies that had not been addressed by the recent review 13…”

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

“…Besides, Reddy et al (Reddy et al, 2011) prepared a series of 2-substituted mercaptobenzimidazole derivatives and reported that compounds 178-180 produced notable antiulcer potentiality at a dose level of 10 mg/kg comparable to omeprazole. Furthermore, compound 181 prevented H + /K + -ATPase enzymatic activity with an IC 50 value of 1.6 × 10 -5 M and compound 182 displayed prominent effects on inhibition of gastric lesions and gastric acid secretion in a dose dependant manner (0.3-30 mg/kg) (Tanaka et al, 2011;Yan et al, 2011). Moreover, some benzimidazole-piperazine conjugated analogues were assessed for their in vivo antiulcer property.…”

Copper containing nanosilica thioalated dendritic material: A recyclable catalyst for synthesis of benzimidazoles and benzothiazoles

“…These compounds are crucial core structures used to produce drugs and materials. They show medicinal activities such as anticancer, antiulcer, antihypertensive, antibacterial, and enzyme inhibition . They have also been applied in dyes, chemosensing, fluorescence, and corrosion science .…”