NATURE INSPIRED BROMOTYROSINE OXIME DERIVATIVES AS ANTI-ALGAE AGENTS AND SMALL MOLECULE INHIBITORS OF THE CHIKUNGUNYA VIRUS

Abstract

SYNTHETIC COMPOUND LIBRARIES OF BROMOTYROSINE DERIVATIVES WERE TESTED FOR ANTI-ALGAE AND ANTI-VIRAL ACTIVITIES AGAINST AMPHORA COFFEAEFORMIS AND THE CHIKUNGUNYA VIRUS RESPECTIVELY. IN THE ANTI-ALGAE STUDY, POTENTIAL COMPOUNDS WERE IDENTIFIED WITH A SINGLE CONCENTRATION CELL ADHESION ASSAY FOLLOWED BY A DOSE-RESPONSE ASSAY TO DETERMINE THE EC50 VALUES (CONCENTRATION THAT RESULT IN 50% DECREASE IN NUMBER OF ATTACHED CELLS). HOWEVER, THE ADHESION ASSAY WAS HAMPERED BY THE POOR SOLUBILITY OF THE COMPOUNDS. ANALYSIS OF THE PHYSICAL PROPERTIES SUGGESTS THAT THE COMPOUNDS SHOULD HAVE CLOGP VALUES SMALLER THAN 3 AND MOLECULAR WEIGHTS LESS THAN 300 TO BE SOLUBLE. IN THE CHIKV STUDY, THE TOXICITIES AND ANTI-VIRAL ACTIVITIES OF THE COMPOUNDS WERE TESTED BY IN VITRO CELL VIABILITY AND ANTI-VIRAL ASSAYS AGAINST THE HUMAN EMBRYONIC KIDNEY (HEK293T) CELL-LINE. STRUCTURAL FEATURES IMPORTANT FOR A POTENT ANTI-VIRAL AND NON-TOXIC COMPOUND WERE IDENTIFIED, LEADING TO LEAD COMPOUND 62 (EC50 4.3 ?M, CC50 >