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

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

Essam M Hussein  1   2 , Munirah M Al-Rooqi  1 , Shimaa M Abd El-Galil  3 , Saleh A Ahmed  1   2
Affiliations

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

Essam M Hussein et al. BMC Chem. .

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.

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Conflict of interest statement

Competing interestsThe author declares that they have no competing interests.

Figures

Fig. 1
Fig. 1
Structural elements of DHFR inhibitors in the DHFR enzymatic active site
Scheme 1
Scheme 1
Synthesis of novel N4-substituted sulfonamide derivatives 5a–p and 6a–p
Fig. 2
Fig. 2
Comparison of the antimicrobial activity of the newly synthesized compounds
Fig. 3
Fig. 3
Comparison of cytotoxic activity of the tested compounds against (A-549) and (MCF-7) cell lines
Fig. 4
Fig. 4
The docking score energy of the tested synthesized compounds
Fig. 5
Fig. 5
Docking of (5-FU) into DHFR
Fig. 6
Fig. 6
Docking of compounds 5g, 5j, 6d and 6h into DHFR
See this image and copyright information in PMC

References

    1. Drews J. Drug discovery: a historical perspective. Science. 2000;287:1960–1964. doi: 10.1126/science.287.5460.1960. - DOI - PubMed
    1. Krátký M, Vinsová J, Volková M, Buchta V, Trejtnar F, Stolaríková J. Antimicrobial activity of sulfonamides containing 5-chloro-2-hydroxy-benzaldehyde and 5-chloro-2-hydroxybenzoic acid scaffold. Eur J Med Chem. 2012;50:433–440. doi: 10.1016/j.ejmech.2012.01.060. - DOI - PubMed
    1. Anjaneyulu R, Anjaneyulu K, Couturier E, Malaisse WJ. Opposite effects of hypoglycemic and hyperglycemic sulfonamides upon ionophore-mediated calcium transport. Biochem Pharmacol. 1980;29:1879–1882. doi: 10.1016/0006-2952(80)90097-0. - DOI - PubMed
    1. Thornber CW. Isosterism and molecular modification in drug design. Chem Soc Rev. 1979;8:563–580. doi: 10.1039/cs9790800563. - DOI
    1. Supuran CT, Scozzafava A. Carbonic anhydrase inhibitors and their therapeutic potential. Expert Opin Ther Pat. 2000;10:575–600. doi: 10.1517/13543776.10.5.575. - DOI

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