ANTI-INFLAMMATORY PROPERTY OF NOVEL ISOINDOLE LEAD COMPOUNDS AND ESTIMATION OF LD50 OF THE MOST ACTIVE ENTITY

Madani A. M., Aimun A. E. Ahmed*, Tilal Elsaman, EI-Hadiyah T. M. and Hatem A. Abdel-Aziz

ABSTRACT

Background: Isoindole derivatives serve as an important source for lead compounds with numerous pharmacological uses. Objectives: The study aimed to investigate the anti-inflammatory property for newly synthesized six isoindole derivatives; TIND-1, TIND-7, TIND-10, TIND-11, TIND14 and TIND-15, and to estimate LD50 of most promising one. Methods: The carrageenan-induced paw edema model in rats used to investigate the anti-inflammatory activity of the tested compounds and to compare between them and the standard drug using inhibition of edema as a pharmacological parameter. Whilst the LD50 was estimated for TIND-7, using OEDC-AOT 425 guideline for acute oral toxicity on rats, in vivo. Results: All tested compounds exhibited various time-dependent anti-inflammatory activity, through different period of time; first hour, significant effect was revealed for TIND-14 (P<0.01) and TIND-15 (P<0.001), whilst at third hour, TIND-7 exhibited 71%, TIND-14 and TIND-15 demonstrated highest activity. Moreover, at fifth hour TIND-7 produced 100% inhibition. The estimated LD50 for the most active compound (TIND-7) was more than 2000 mg/kg. Conclusion: All tested compounds showed variety of anti-inflammatory activity against carrgenan-induced paw edema on rats, in vivo, however TIND-7 was the most promising compound ever, with reasonable margin of safety estimated as LD50.

Keywords: Anti-inflammatory, Isoindole, Paw-edema, Diclofenac, LD50, Protocol 425.