Design by Synthesis & Biological Screening of Some Hydroxamic Acid Analogues

Abstract

Salicylhydroxamic acid, isonicotinohydroxamic acid, and paminobenzohydroxamic acid were prepared by the reaction of hydroxylamine and methylsalicylate, ethylisonicotinate, and ethyl-p-amino benzoate, respectively. The hydroxamic acids prepared were identified by their characteristic reactions with FeCl3, their melting points, nitrogen contents, and infrared spectra. These hydroxamic acids were assessed for their potential antibacterial activity. Isonicotinohydroxamic acidand p-aminobenzohydroxamic acid displayed a very week activity against the E. coli, Ps. aeruginosa, B. subtilis, and S. aureuswhile salicylhydroxamic acid did no show such activity. Salicylhydroxamic acid was tested for anti-inflammatory, analgesic, and antipyretic activities. Aspirin was selected as the reference antiinflammatory drug. Salicylhydroxamic acid caused 2.78 ± 3.81 % inhibition of cotton pellet granuloma formation in rats with a dose of 130 mg/kg while aspirin caused 11.10 ± 4.56 % reduction. With a dose of 260 mg/kg, salicylhydroxamic acid showedsimilar reduction to that obtained with the same dose of aspirin. The reduction with salicylhydroxamic acid was 20.37 ± 9.24 % compared to 23.52 ± 8.12 % for aspirin. With a dose of 400 mg/kg, the reduction ingranuloma formation caused by salicylhydroxamic acid was 41.42 ± 5.53 % and that caused by aspirin was 60.12 ± 3.81 %. Both aspirin and salicylhydroxamic acid reduced the body temperature of yeast-induced hyperthermia in rats. In addition, salicylhydroxamic acid caused 40.83 % analgesia while aspirin caused 84.06 % analgesia as indicated by quantal response in a hot plate experiment. p-Aminobenzohydroxamic acid was tested for local anesthetic activity. The compound showed a local anesthetic effectas assessed by foot withdrawal reflex model. The local anesthetic activity of paminobenzohydroxamic acid was similar to that of benzocaine in high dosage. Doses of 1000 µg, 200 µg, and 40 µg of p-aminobenzohydroxamic acid caused 40.31 ± 0.74 %, 56.38 ± 0.87 %, and 33.93 ± 0.80 % delay in food withdrawal reflex, respectively.On the other hand, benzocaine caused 44.12 ± 1.2 %, 25.74 ± 0.91 %, and 13.48 ± 0.96 % delay in food withdrawal reflex at doses of 1000 µg, 200 µg, and 40 µg, respectively.