Cytotoxicity, Docking Study of New Fluorinated Fused Pyrimidine Scaffold: Thermal and Microwave Irradiation Synthesis

Title:Cytotoxicity, Docking Study of New Fluorinated Fused Pyrimidine Scaffold: Thermal and Microwave Irradiation Synthesis

Volume: 17 Issue: 5

Author(s): Alaa M.A. Alnaja, Thoraya A. Farghaly*, Heba S.A. El-zahabi and Mohamed R. Shaaban

Affiliation:

• Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah, Almukaramah,Saudi Arabia

Keywords: Anticancer activity, fused pyrimidines, aminopyrazoles, microwaves, structure-activity relationship (SAR), docking study.

Abstract:

Background: Azolopyrimidines are imposed on the arena of drugs treated for cancer. The urgent need to discover new selective anticancer agents, paved the way to explore the antitumor significance of such fused systems. From the synthetic point of view, Microwave facilitated technique for synthesis is very strongly associated with green method in chemistry field.

Aim: Our aim is to synthesize bioactive compounds using docking simulation run by MOE program to explore the binding mode of the most active enzyme inhibitor among the target compounds.

Methods: In addition to the use of conventional heating, the MARS system of CEM utilized for Microwave irradiation that is equipped with a multi-mode platform with a magnetic stirring plate and a rotor that allows the parallel processing of many vessels per batch. All the synthesized compounds were tested for their anticancer activity against hepatic cancer (HepG-2), breast cancer (MCF-7) and colon cancer (HCT-116). Screening against the cancer cell lines was performed, using doxorubicin as a reference drug. Docking studies were conducted using MOE software.

Results: A novel series of fluorinated fused-pyrimidine namely, pyrazolopyrimidine, triazolopyrimidine and pyrimidobenzimidazole were designed and synthesized conventionally and under microwave irradiations. The mechanistic pathways as well as the structure of all products were debated and demonstrated based on all possible spectral data. In-vitro examination of the novel prepared derivatives versus the three different human cancer cell lines [hepatic cancer (HepG-2), breast cancer (MCF-7) and colon cancer (HCT-116)] was evaluated to estimate their actual activity.

Conclusion: We have developed a simple, facile, and efficient procedure for the formation of new series of azolopyrimidines. All spectra of all products were investigated deliberately to confirm their structures. The anti-cancer activity has been examined against three cancer cell lines e.g. HepG-2, MCF-7 and HCT116. Molecular modeling study was carried out in order to rationalize the in vitro anti-tumor results.

Cite this article as:

Alnaja M.A. Alaa , Farghaly A. Thoraya *, El-zahabi S.A. Heba and Shaaban R. Mohamed , Cytotoxicity, Docking Study of New Fluorinated Fused Pyrimidine Scaffold: Thermal and Microwave Irradiation Synthesis, Medicinal Chemistry 2021; 17 (5) . https://dx.doi.org/10.2174/1573406416666191216120301

DOI https://dx.doi.org/10.2174/1573406416666191216120301	Print ISSN 1573-4064
Publisher Name Bentham Science Publisher	Online ISSN 1875-6638