STUDIES ON THE DESIGN, SYNTHESIS AND ANTITUBERCULAR ACTIVITY OF SOME NEW QUINAZOLINONE DERIVATIVES

Quinazolinone derivatives are the versatile nitrogen containing heterocyclic compounds displaying a wide variety of biological and pharmacological activities like antibacterial, anthelmintic,neuroleptic,antitubercular,platelet,antiaggregating,antifungal,anticancer,anti-inflammatory,antiviral,CNSdepressant activity,antiparkinson,bronchodilator etc. Recently several scientists have elucidated that Quinazolinone system possesses variable sites like position 2 and 3 which can be suitably modified to yield new potent chemotherapeutic and pharmacotherapeutic agents. Further, Schiff bases are use as substrate in the preparation of number of industrial and biologically Active compound via ring closure, cyclo addition and replacement reactions.Morever,Schiff b a s es d e r i v e d from various heterocycles have been reported to posses cytotoxic, anticonvulsant, antiproliferative,antimicrobial, anticancer and antifungal activities. In view of the above mentioned facts and in continuation of our interest in the synthesis of heterocycles to identify new candidate, that may be value in designing new, potent, selective and less toxic chemotherapeutic agents, the synthesis of some novel structure hybrids incorporating suitably substituted quinazolinone moiety with long aliphatic dicarboxylic acids hydrazides and finally converting them to Schiff bases by reacting with substituted benzaledhydes to yield title compounds. These are then evaluated for antitubercular activity by Micro plate alamar blue assay method(MABA) and MIC were determined for each drug.During the present investigation 1,3,4-benzoxazinone was prepared from anthranilic acid and acetic anhydride by known method. Various dihydrazides were prepared from aliphatic α, ω-aliphatic dicarboxylic acids by following literature method. N-3 substituted quinazolinone derivatives were prepared from the equimolar reaction of 1,3,4-benzoxazinone with various dihydrazides to yield the compounds 1AB1 to 1AB5. These are then reacted with substituted benzaledhydes to form Schiff bases 2B1 to 2B5. The homogeneity of all the derivatives was established by TLC technique. The structures of the compounds were successfully established by means of IR, Proton NMR and Mass spectral studies.All the compounds were evaluated f o r a nti tu b erc ula r activity against Mycobacterium tuberculosis H37Rv by micro plate blue assay method (MABA).One of the compound 2B5 has shown excellent antitubercular property by having lowest MIC of 3.125µg/ml were as the other compounds also exhibited significant growth inhibiting properties against the mycobacterium tested. Key words: Quinazolinone, Mycobacterium tuberculosis, antitubercular activity.