Abstract

ENHANCED CYTOTOXIC ACTIVITY OF NOVEL SYNTHESIZED SULFADIAZINE DERIVATIVES BOUND LIPOSOMES TOWARDS BREAST CANCER CELL LINE: COMPARATIVE STUDIES WITH DIFFERENT CELL LINES

Tareq Said Abd El. Rashed*, Marina Nabil Habib and Marina Mamdouh Makram

ABSTRACT

The present study aims to evaluate the cytotoxic efficacy of sulfadiazine derivative N-(4,6-bis (4-methoxyphenyl) pyrimidin-2-yl) benzenesulfonamide (G16) and its conjugation with L-α-Phosphatidylethanolamine (Cephalin) liposomes through detecting the possible effects of these compounds on the DNA damage of a human colon (CaCo2), breast (MCF-7) and pancreatic (PANC-1) cell lines carcinoma. The IC50 value for G16-doped liposomes in cytotoxic assay with MCF-7 treated cells was 24 μg/ml, while for MCF-7 treated cells with free G16 was 450 μg/ml. Using of liposomes increased the anticancer activity of G16 by 20 times than free G16. The IC50value for G16-doped liposomes in cytotoxic assay with CaCo2 treated cells was 62 μg/ml, while for PANC-1treated cells was 58 μg/ml. IC50value for CaCo2, MCF-7 and PANC-1cell lines treated with free G16 was 296, 450 and 420 μg/ml, respectively. The results indicated that all comet assay parameters for the G16-loaded liposomes treated cells were significantly increased (P < 0.05) compared to free G16 and control values. The results reveal a higher intensity of comet tail in MCF-7 cells treated with G16-loaded liposomes than those treated with free G16. Such high intensity relative to head indicates the presence of several double-strand breaks. The molecular combination between G16 and liposomes was characterized. The encapsulated G16 is probably associated with the lipid bilayers which results in the broadening and shift to higher temperature 143.7 C of the main peak of pure liposomes that exists at 141.2C. FTIR study revealed structure alterations in vesicles after the encapsulation of G16 into liposomes.

Keywords: G16; Liposomes; DLS; DSC; FTIR; Comet assay; Cytotoxicity.