Design, synthesis, and biological evaluation of novel N 4 -substituted sulfonamides: acetamides derivatives as dihydrofolate reductase (DHFR) inhibitors

Essam M Hussein; Munirah M Al-Rooqi; Shimaa M Abd El-Galil; Saleh A Ahmed

doi:10.1186/s13065-019-0603-x

Design, synthesis, and biological evaluation of novel N ⁴ -substituted sulfonamides: acetamides derivatives as dihydrofolate reductase (DHFR) inhibitors

BMC Chem. 2019 Jul 11;13(1):91. doi: 10.1186/s13065-019-0603-x. eCollection 2019 Dec.

Authors

Essam M Hussein^{1

2}, Munirah M Al-Rooqi¹, Shimaa M Abd El-Galil³, Saleh A Ahmed^{1

2}

Affiliations

¹ 1Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah, 21955 Saudi Arabia.
² 2Chemistry Department, Faculty of Science, Assiut University, Assiut, 71516 Egypt.
³ 3Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-azhar University, Nacr City, Cairo, Egypt.

Abstract

Background: Sulfonamide derivatives are of great attention due to their wide spectrum of biological activities. Sulfonamides conjugated with acetamide fragments exhibit antimicrobial and anticancer activities. The inhibition dihydrofolate reductase (DHFR) is considered as one of the most prominent mechanism though which sulfonamide derivatives exhibits antimicrobial and antitumor activities.

Results: In this study, a new series of 2-(arylamino)acetamides and N-arylacetamides containing sulfonamide moieties were designed, synthesized, characterized and assessed for their antimicrobial activity and screened for cytotoxic activity against human lung carcinoma (A-549) and human breast carcinoma (MCF-7) cell lines. A molecular docking study was performed to identify the mode of action of the synthesized compounds and their good binding interactions were observed with the active sites of dihydrofolate reductase (DHFR).

Conclusion: Most of the synthesized compounds showed significant activity against A-549 and MCF-7 when compared to 5-Fluorouracil (5-FU), which was used as a reference drug. Some of these synthesized compounds are active as antibacterial and antifungal agents.

Keywords: Acetamides; Anticancer; Antimicrobial; DHFR inhibitors; Molecular docking; Structure–activity relationship (SAR); Sulfonamide.