Evaluation of pharmacological activities of 1,3,4-oxadiazole derivatives

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are being employed since decades to treat inflammation, pain as well as fever. Because of continuing research in this field, numerous NSAIDs have become readily available for treatment of diverse fonns of inflammation-linked diseases. However, there is still need to develop more efficient and safe drugs. In order to develop new and safer therapeutic molecules, heterocyclic compounds including 1,3,4-oxadiazole have become an important core of attention. Although compounds with 1,3,4-oxadiazole nuclei have a broad range of pharmacological activities including anti-inflammatory, analgesic, antibacterial, antifungal, antipyretic, antidiabetic, antiviral, antihypertensive, anticonvulsant and anxiolytic-hypnotic activities, but anti-inflammatory, antimicrobial and anticancer activities are at the forefront of research in the past decade. These observations lead us to evaluate eight new derivatives of 1 ,3,4-oxadiazole with thiol moiety at 2 and different substituents at 5 position for their anti-inflammatory, analgesic, antipyretic, antimicrobial and glucosidase inhibition potential. Anti-inflammatory activity was estimated by in-vivo carrageenan-induced paw edema method in mice as well as by in vitro membrane stabilization method. The results so acquired showed that treatment with 5-( 1-(2-chlorophenoxy)ethyl)-1 ,3,4-oxadiazole-2-thiol (F) and 5-(1-(4- chlorophenoxy)ethyl)-1,3,4-oxadiazole-2-thiol (G) are effective against inflammation. These compounds are also effective against fomlalin-induced analgesia in mice and yeast-induced pyrexia in rats. The compounds were further screened by performing in vitro antimicrobial and glucosidase inhibition assay. In antimicrobial assay, among all the screened compounds, 5-dodecyl-l,3,4-oxadiazole-2-thiol (B) and 5- (( 4chlorophenoxy)methyl)-1 ,3,4-oxadiazole-2-thiol (G) were found to have significant (P~O.OOl) antimicrobial activity against Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE) as compared to standard antibiotics in clinical use. 5-(2,4,6-trimethoxyphenyl)-1,3,4- oxadiazole-2-thiol (E) and 5-(naphthalen-l-yl)-1,3,4-oxadiazole-2-thiol (H) were found to be potent inhibitors of glucoSidase enzyme. Moreover, the active compounds were observed having no significant toxicity against brine shrimps in lethality assay and in in-vivo acute animal testing. These observations advocate their use as a lead for developing new therapeutic agents. Nevertheless, additional research is required to find out the exact mechanism(s) of anti-inflammatory, analgesic, antipyretic and viii antimicrobial activities of synthetic compounds by using methods in molecular phannacology. After that, the real efficacy and safety can be ascertained within patients by following approved protocols by FDA. Key words: Anti-inflammatory, analgesic, anti-pyretic, anti-bacterial, anti-fungal, 1,3,4-oxadiazole.