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 (p53^Y220C and p53^Y220S) 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.

Keywords:

• p-methoxyphenyl maleanilic acid
• cytotoxicity
• ^99mTc-radiolabeling
• biodistribution
• docking study
• cancer monitoring

Acknowledgments

The authors would like to acknowledge Prof. M. Zayed, Chemistry Department, Faculty of Science, Cairo University, for his contribution in the preparation and characterization of MPMA.

Disclosure statement

The authors declare that they have no conflicts of interest to disclose. Moreover, this research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Notes on contributors

Nourihan S. Farrag

Nourihan S. Farrag, Assistant Professor of Radiopharmaceutics, Labeled Compounds Department, Hot Labs. Center, Egyptian Atomic Energy Authority, Cairo, Egypt.

S. I. Khater

S. I. Khater, Assistant Professor of Radiochemistry, Radioactive Isotopes and Generators Department, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo, Egypt.

Fatma S. M. Hassan

Fatma S. M. Hassan, Professor of Chemistry, Chemistry Department, Aswan University, Aswan, Egypt.

Abeer M. Amin

Abeer M. Amin, Professor of Radiochemistry, Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo, Egypt.