Abstract

SYNTHESIS AND IN VITRO ANTICANCER ACTIVITY OF NOVEL 5- [(1-BENZYL-1H-1,2,3-TRIAZOL-4-YL)METHYL]-3-METHYL-5HISOXAZOLO[ 5’,4’:5,6]PYRIDO[2,3-b]INDOLES

E. Rajanarendar*, P. Venkateshwarlu, S. Ramakrishna, K. Goverdhan Reddy, M. Nagi Reddy, Y.N. Reddy

ABSTRACT

Cancer is a deadly disease in the world today and causes more deathsthan any other disease. Inspite of the extensive efforts, the managementof human malignancies still contains a major challenge forcontemporary medicinal chemistry. There has been an urgent need fordevelopment of more efficient anticancer agents with minimal sideeffects. Neocryptolepine an alkaloid isolated from cryptolepissanguinoleta is found to display strong in vitro and in vivo cytotoxicactivities. In view of this, the present study was designed to synthesizesome novel derivatives of 1,2,3-triazolyl isoxazolo[5’,4’:5’,6] pyrido[2,3-b] indoles which are bioisosteric with neocryptolepine derivatives. The synthesis of titlecompounds was accomplished by condensation of 3,5-dimehtyl-4-nitroisoxazole withdifferent N-propargyl isatins, in ethanol in the presence of piperidine, followed by reductivecyclization with iron powder in acetic acid, finally [2+3] cycloaddition of benzyl azide toC=C in presence of saturated CuSO4 solution-Cu turnings in ethanol. The newly synthesizedcompounds were screened for their in vitro anticancer activity by using MTT assay method.The results indicate that these compounds have considerable in vitro anticancer activity. Outof the eight derivatives, compound 5b and 5c have shown potential anticancer activity ascompared with the reference compound Cisplatin.

Keywords: 1,2,3-Triazolyl isoxazolo[5’,4’:5,6]pyrido[2,3-b]indoles, reductive cyclization, [2+3] cycloaddition, anticancer activity.