Synthesis and molecular docking against dihydrofolate reductase of novel pyridin-N-ethyl-N-methylbenzenesulfonamides as efficient anticancer and antimicrobial agents

Debbabi, Khaled; Bashandy, Mahmoud S.; Al‐Harbi, Sami A.; Aljuhani, Enas; Al-Saidi, Hamed M.

doi:10.1016/j.molstruc.2016.11.048

Cited by 15 publications

(4 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2017, Debbabi et al described some new pyridin-N-ethyl-N-methylbenzenesulfonamides as efficient anticancer agents against the MCF-7 breast cancer cell line, showing IC 50 values in the range of 7.68-22.7 µM with a selectivity index in the range of 4.71-9.72. Docking studies confirmed the interaction of 21 , the best compound of the series in terms of activity, with DHFR active sites (PDB ID: 4DFR) [55].…”

Section: Inhibitors Of Human Dhfr Under Preclinical Investigationmentioning

confidence: 95%

DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents

et al. 2019

View full text Add to dashboard Cite

Dihydrofolate reductase inhibitors are an important class of drugs, as evidenced by their use as antibacterial, antimalarial, antifungal, and anticancer agents. Progress in understanding the biochemical basis of mechanisms responsible for enzyme selectivity and antiproliferative effects has renewed the interest in antifolates for cancer chemotherapy and prompted the medicinal chemistry community to develop novel and selective human DHFR inhibitors, thus leading to a new generation of DHFR inhibitors. This work summarizes the mechanism of action, chemical, and anticancer profile of the DHFR inhibitors discovered in the last six years. New strategies in DHFR drug discovery are also provided, in order to thoroughly delineate the current landscape for medicinal chemists interested in furthering this study in the anticancer field.

show abstract

Section: Inhibitors Of Human Dhfr Under Preclinical Investigationmentioning

confidence: 95%

DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Various strategies have been implemented to discover new antimalarial drugs [6]. Some researchers try to find a new antimalarial drug base on the molecular docking study [7][8][9][10][11][12]. Binding free energy between ligand-receptor of the best pose (conformation) resulted from docking procedure are then calculated via Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) approach [13][14].…”

Section: ■ Introductionmentioning

confidence: 99%

Docking of New Designed Compounds Derived from 1,6-Dihydro-1,3,5-triazine-2,4-diamine Toward Quadruple Mutant Plasmodium Dihydrofolate Reductase

2019

View full text Add to dashboard Cite

Resistance to the traditional antifolates is now widespread in Plasmodium falciparum and Plasmodium vivax. To find the interaction model of some compounds derived from 1,6-dihydro-1,3,5-triazine-2,4-diamine, molecular docking technique was carried out using these compounds ligand and pDHFR as the receptor. Complex ligand and the receptor from Protein Data Bank (PDB ID 1J3K) were chosen as an interaction model between a ligand and its receptor. Each compound was optimized using ab initio methods with 6-311G basis set. Partial charges of ligand were added using AM1-BCC methods. Each ligand was docked to the receptor utilizing Dock6 software. Theoretical prediction based on the binding energy between these compounds as the ligand with pDHFR as receptor resulted in 1 compound, namely 6,6-dimethyl-1-[3-(2-chloro-4,5-dibromophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine possessing binding affinity better than that of WR99210 which was known to have good antimalarial activity.

show abstract

“…The compounds showed hydrogen bond interaction with different amino acid residues like Asp21, Ser59 and Glu30. [59] El-Naggar et al synthesized number of 1,3,4-thiadiazole conjugates (Scheme 42) and tested for in vitro DHFR inhibition, antimicrobial and anticancer activity. Compound 218 was most potent among all synthesized derivatives and also exhibited comparable anticancer activity against all evaluated cancer cell lines as compared to standard drug doxorubicin.…”

Section: Chemistryselectmentioning

confidence: 99%

An Insight into Synthetic Strategies and Recent Developments of Dihydrofolate Reductase Inhibitors

et al. 2021

View full text Add to dashboard Cite

The dihydrofolate reductase (DHFR) is a significant target in cancer, microbial infection, fungal infection, malaria, leishmaniasis, and tuberculosis, among other diseases. The DHFR gene was discovered in prokaryotes and eukaryotes in the late 1950s and is found in all dividing cells. DHFR inhibitors are used for a variety of medicinal purposes. Increased resistance to therapeutic agents such as anticancer, antibiotic, anti‐tuberculosis, and antifungal sparked interest in the development of potent, broad‐spectrum medicines to address the issues. DHFR is a critical target in the development of innovative solutions to address the issues. Methotrexate, trimethoprim, sulfonamides, pyrimethamine, aminopterin, methotrexate, edatrexate, and pralatrexate are only a few of the medications that target DHFR. These medications are known as DHFR inhibitors. These inhibitors block the enzyme dihydrofolate reductase, resulting in a folic acid synthesis pathway that is compromised. The DHFR is involved in the conversion of dihydrofolate to tetrahydrofolate. Purine, pyrazole, pyrimidine, triazole, oxadiazole, and other heterocyclic motifs have shown to have a potential effect on the DHFR. In the medicinal chemistry community, a better understanding of the so‐called enzyme and biochemical underpinnings responsible for enzyme selectivity has led to the development of improved, unique, and new treatments. Several researchers are working on DHFR inhibitors intensely, using a variety of synthetic techniques, molecular modelling, mechanistic studies, in‐vitro and in‐vivo biological evaluations, and structure‐activity relationships (SAR). This review, compiles the findings of several research groups during the last five years. The molecular biology of DHFR, its biosynthetic pathway, and the powerful structure of DFHR inhibitors discovered during the search are all included in this review. The study also includes the latest developments in synthetic methods, molecular docking, and structure‐activity relationships.

show abstract

Synthesis and molecular docking against dihydrofolate reductase of novel pyridin-N-ethyl-N-methylbenzenesulfonamides as efficient anticancer and antimicrobial agents

Cited by 15 publications

References 39 publications

DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents

DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents

Docking of New Designed Compounds Derived from 1,6-Dihydro-1,3,5-triazine-2,4-diamine Toward Quadruple Mutant Plasmodium Dihydrofolate Reductase

An Insight into Synthetic Strategies and Recent Developments of Dihydrofolate Reductase Inhibitors

Contact Info

Product

Resources

About