New heterocyclic derivatives of benzimidazole with germicidal activity--IX--HPLC detection of 5-fluoro-2-(5'-nitro-2'-furyl)benzimidazole (F-O-NO2) in biological samples.

The HPLC technique for the isolation and quantitation of 5-fluoro-2-(5'-nitro-2'-furyl)benzimidazole (F-O-NO2), previously described by the same Authors, in biological samples from mice is reported. Evidence is given that the highest biological concentration and the time needed for reaching it depend both on the dose and on the administration route. In fact, almost the same maximal biological concentration of F-O-NO2 (about 0.18 micrograms/mouse) is reached after 60 min from either 40 mg/Kg IP or 200 mg/Kg os drug administration, whereas the maximal biological concentration of F-O-NO2 (5.75 micrograms/mouse) is reached after 30 min from 120 mg/Kg IP drug administration.

New heterocyclic derivatives of benzimidazole with germicidal activity. IV--In vivo anticandida activity of 5-fluoro-2-(5'-nitro-2'-furyl) benzimidazole (F-O-NO2).

We have studied the possible in vitro and in vivo antibacterial activity of 5-fluoro-2-(5'-nitro-2'-furyl)benzimidazole (F-O-NO2). Our data demonstrate that F-O-NO2 is able to inhibit the in vitro growth of different mycetes and bacteria, including Candida albicans and Cryptococcus neoformans. We also tested the possible in vivo activity against Candida albicans. The results clearly show that treatment with F-O-NO2 is able to significantly augment the survival of all treated animals; in particular, when injected i.p. at the dose of 120 mg/kg, 30' or 1 hr after Candida albicans challenge, it givens a MST (Medium Survival Time) longer than 60 days. These data demonstrate that F-O-NO2 has antibacterial and antimycotic activity.

[N1-substituted 1H-indazole-3-ethyl carboxylates and 1H-indazole-3-hydroxamic acids]. / 1H-Indazole carboxylates d'éthyle-3 N1-substitués et acides 1H-indazole hydroxamiques-3.

Sixty five new derivatives of ethyl-1H-indazole-3-carboxylate are described; they contain in N1 various aliphatic or aromatic acyl radicals. Moreover halogens or methyl groups are present as substituents at the 5 position or methyl groups at 5,6. The synthesis of seven 1H-indazole-3-hydroxamic acids, substituted at 6 and/or 5 as above, is also described. Some of the synthesized derivatives have preliminarily been tested on rats to investigate acute toxicity, possible antiarthritic effects on primary or secondary arthritis, and their action on weight gain. Some of these indazole derivatives had an antiarthritic effect at doses much lower than the toxic ones; among the compounds tested up to now, the ethyl-5-methyl-N1-p-chlorobenzoyl-1H-indazole-3-carboxylate gave the best results. Weight gain as not affected by any of the examined compounds.