Bioactive fluorenes. part I. Synthesis, pharmacological study and molecular docking of novel dihydrofolate reductase inhibitors based-2,7-dichlorofluorene

Essam M Hussein; Reem I Alsantali; Shimaa M Abd El-Galil; Rami J Obaid; Ahmed Alharbi; Mohamed A S Abourehab; Saleh A Ahmed

doi:10.1016/j.heliyon.2019.e01982

Bioactive fluorenes. part I. Synthesis, pharmacological study and molecular docking of novel dihydrofolate reductase inhibitors based-2,7-dichlorofluorene

Heliyon. 2019 Jun 26;5(6):e01982. doi: 10.1016/j.heliyon.2019.e01982. eCollection 2019 Jun.

Authors

Essam M Hussein^{1

2}, Reem I Alsantali^{1

3}, Shimaa M Abd El-Galil⁴, Rami J Obaid¹, Ahmed Alharbi¹, Mohamed A S Abourehab^{5

6}, Saleh A Ahmed^{1

2}

Affiliations

¹ Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, 21955, Makkah, Saudi Arabia.
² Chemistry Department, Faculty of Science, Assiut University, 71516, Assiut, Egypt.
³ Department of Pharmaceutical Chemistry, Pharmacy College, Taif University, 888, Taif, Saudi Arabia.
⁴ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (girls), Al-azhar University, Nacr City, Cairo, Egypt.
⁵ Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
⁶ Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt.

Abstract

In this study, a new series of 2,7-dichloro-4-(2-substituted-amino acetyl)fluorene derivatives were synthesized, characterized and evaluated for their antimicrobial activity and screened for cytotoxic activity against human lung carcinoma (A-549) and human breast carcinoma (MCF-7) cell lines. Most of the synthesized compounds displayed significant activity against A-549 and MCF-7 cell lines when compared to 5-fluorouracil (5-FU), which was used as a reference drug. In addition, some of these reported novel compounds exhibited promising antibacterial and antifungal properties. A molecular docking study was performed to identify the mechanism of action of the synthesized compounds, which suggested binding interactions with the active sites of dihydrofolate reductase (DHFR).

Keywords: Anti-cancer; Antimicrobial; DHFR inhibitors; Fluorene; Molecular docking; Organic chemistry.