engleski

Biological evaluations of amidine and amidoxime substituted heterocycles with 1, 2, 3-triazolyl spacer

Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hybrid compound with improved affinity and efficacy, when compared to the parent drugs.[1] This approach was adopted for design and synthesis of diversified library of benzofused heterocycle–1, 2, 3-triazole conjugates to evaluate their cytostatic and antibacterial activities. Thus, coumarin–1, 2, 3-triazole– benzofused heterocycle hybrids emerged as the class of compounds exhibiting the highest antiproliferative activity.[2] While 5, 6- disubstituted furo[2, 3-d]pyrimidine-2-one derivative exhibited selective activity against hepatocellular carcinoma (HepG2) and cervical carcinoma (HeLa) cells with higher potencies than the reference drug 5-fluoruracil, benzothiazole– 1, 2, 3-triazole–coumarin hybrid showed potent anti- Moraxella catarrhalis activity.[3, 4] Novel hybrids of aromatic nitrile and heterocycle linked via 1, 2, 3-triazole scaffold were syntesized by regioselective Cu(I)-catalyzed azide-alkyne 1, 3- dipolar cycloaddition. Nitrile derivatives were used as precursors for synthesis of amidine and amidoxime substituted selected heterocycles. Results of antiproliferative evaluations for newly synthesized compounds on human tumor and normal cell lines will be presented.

1, 2, 3-triazole, amidine, amidoxime, antitumor activity

nije evidentirano