Investigation for anticancer activity of the newly synthesized p-Methoxyphenyl maleanilic acid and the diagnostic property of its 99mTc-analogue.

ABSTRACT

PURPOSE: The limitations of the current chemotherapeutics are the main rational to develop and/or explore new anticancer agents and radiolabeled analogues for cancer early diagnosis. MATERIALS AND METHODS: The newly synthesized p-methoxyphenyl maleanilic acid (MPMA) was prepared, characterized and investigated for its anticancer activity. MPMA screened in-vitro against human hepatocellular carcinoma (HepG-2), human colon carcinoma (HCT-116) and human breast carcinoma (MCF-7) cell lines. Furthermore, the in-vivo screening was performed by radiolabeling of MPMA with technetium-99m (99mTc) and investigating its biological distribution in normal mice and solid tumor models. Moreover, MPMA and its radiolabeled analogue were docked to Y220C and Y220S mutants of p53 (p53Y220C and p53Y220S) in an effort to confirm their affinity to cancer as well as to investigate, virtually, the mechanism of action of MPMA. RESULTS: The results revealed significant potency of MPMA against HepG-2 cell line (IC50 = 56.2 ± 1.5 µg/mL) if compared to HCT-116 (IC50 = 89.9 ± 1.8 µg/mL) and MCF-7 (IC50 = 104 ± 2.7 µg/mL) cell lines. The radiolabeling yield was optimized to be 90.2 ± 2.1%. The radiolabeled MPMA showed a good localization in the site of solid tumor (15.1 ± 1.6%ID/g) at 2 h post intravenous administration to the tumor bearing mice. CONCLUSIONS: Collectively, the findings confirmed the potential anticancer activity of MPMA and the possible use of 99mTc-MPMA for cancer diagnosis and monitoring.