SYNTHESIS AND BIOLOGICAL EVALUATION OF 1,3,4-OXAZOLE SUBSTITUTED NOVEL COUMARIN DERIVATIVES

Raveendran K. C.*

Heterocyclic compounds have shown to possess deep impact on biological activities like antitumor, anti-im-inflammatory, Antimicrobial, antiviral etc activities. A number of nitrogen containing heterocyclic groups are present in many of the biologically active compounds. Hence it was a subject of interest to synthesize and study some new heterocyclic derivatives. The nucleus selected for the work is a combination of two hetero aromatic molecules of Coumarin and 1,3,4-oxadiazole.Accordingly,the synthesize were carried out either conventionally as well as Microwave assisted method. There are numerous reports in the literature about the wide spectrum of activities possessed by these versatile lead molecules in pharmaceutical development. So I was synthesized 25 different classes of 1,3,4-oxadiazole derivatives of Coumarin and 10 of them found biologically which were selected for research work. They are CX1, CX3, CX6, CX8, CX10, CX13, CX15, CX18, CX19,CX21and found pharmacologically suitable. The acute toxicity of synthesized oxadiazole derivative were determined by Brine Shrimp Lethality assay. The LD50 values of the compounds were found to be in the range of 400-600μg/ml. The compounds CX1, CX6, CX8 and CX10 were selected for cytotoxicity studies against breast cancer cell and fibrosarcoma cell line. The compound CX8 and CX10 showed better inhibition than other analogues. As the compounds CX1, CX8, CX13 and CX21 showed highest glide scores on docking studies, these analogues were tested for Antitubercular activity. It was found that the analogue CX8 and CX1 showed better activity against the organism. The derivatives CX3 and CX 18 were selected for antibacterial screening according to PASS value. The analogue CX3 was found better inhibition of growth of both gram positive and gram-negative organisms. The derivatives CX3 and CX18 were subjected to antifungal screening with Candida albicans and Aspergillus Niger. The Analogue CX3 was found to exhibit better inhibition of proliferation at concentration 400 μg/ml and Anthelmintic activity CX3 was found higher anthelmintic activity.