engleski

Biological activity of novel primaquine-cinnamic acid conjugates of the acylsemicarbazide type

Considering the individual biological and medicinal importance of primaquine (PQ) and cinnamic acid derivatives (CADs), we wanted to explore biological significance of novel conjugates combining both moieties in single entities. Here we report the results of antiproliferative, antiviral and antioxidative evaluation of new PQ-CAD hybrids 1a-k in which PQ and CADs were connected by acylsemicarbazide groups, built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs.[1] Their antiproliferative activity was evaluated in vitro on five types of human tumor cell lines: lymphoblastic leukemia (CEM), cervical carcinoma (HeLa), lung carcinoma (NCI- H460), colon carcinoma (SW 620), breast carcinoma (MCF-7) and murine lymphocytic leukemia (L1210), and compared with the standard anticancer drugs and PQ. All new hybrids were more or less active against all the tested cell lines in low micromolar concentrations and very active against MCF-7. Compounds bearing methoxy, chloro or benzodioxole substituents showed high selectivity and activity against MCF-7 in micromolar scale and p-CF3 in nanomolar concentration. Most of them bear substituents in para position. Compounds 1a–k were evaluated against a broad variety of viruses (herpes simplex virus type 1 (KOS), herpes simplex virus 2 (G), herpes simplex virus 1 TK–(KOS) ACVr , vaccinia virus, adenovirus 2 and human coronavirus (229E) in HEL cell cultures) and their activities were compared with reference drugs. CF3 derivatives showed selective antiviral activity against human coronavirus at concentrations which did not alter normal cell morphology. Two different antioxidant assays were used to evaluate antioxidant potentials of PQ-CADs: interaction with DPPH free radical and AAPH. For the majority of derivatives, DPPH- reducing ability was concentration and time dependent. CF3, dimethoxy and chloro derivatives showed the highest DPPH-reducing ability, while unsubstituted, methoxy, benzodioxole, p-Cl and m-CF3 derivatives exerted the highest anti- lipid peroxidation activity (83–89%). Dimethoxy derivative was the most potent LOX inhibitor.

primaquine ; cinnamic acid derivatives ; acylsemicarbazide ; antiproliferative activity ; antiviral activity ; antioxidative activity

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