Synthesis, characterization and crystal structures of two novel sulfa drug Schiff base ligands derived sulfonamide and molecular docking study

Compounds bearing and amino acid moieties are considered the basis for sulfa drug development. The synthesis of 4-methylphenylsulphamoyl acids and the evaluation of their pharmacological activities are reported. The synthesis of these compounds was accomplished by the reaction of various acids and 4-methyl chloride in basic aqueous solution. Structures were confirmed by FTIR, 1HNMR, 13CNMR spectra and elemental analytical data. Molecular docking interactions of the analogues were determined using PyRx. In the in antimicrobial activity analysis, compounds 1, 3, 5and 7 had antimicrobial inhibitory concentration range of 0.5-1.0mg/ml comparable with 0.1-2.0mg/ml of and . In the in anti-oxidant activity study compounds 1, 2and 6displayed half-maximal inhibitory concentrations (IC50) of 1.104±0.001 /ml, 1.159±0.002µg/ml and1.240±0.001µg/ml respectively comparable with 0.999±0.002µg/ml of acid. In the molecular docking study, compound 4 had a strong 2D binding interaction with II amino acid residue and compounds 1, 3, 4, 5, 6 and 7 had in antimicrobial, anti-oxidant, and antimalarial properties similar to their standard drugs. Considering the outstanding pharmacological properties and their strict compliance with Lipinski’s rule, the synthesized 4-methylphenylsulphamoyl analogues could be considered as antimicrobial, antimalarial, and anti-oxidant drug candidates.

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Synthesis, Anti-proliferative Activity, and Molecular Docking Study of New Series of 1,3-5-Triazine Schiff Base Derivatives

Molecules ◽

10.3390/molecules25184065 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4065

Author(s):

Hessa H. Al Rasheed ◽

Azizah M. Malebari ◽

Kholood A. Dahlous ◽

Darren Fayne ◽

Ayman El-Faham

Keyword(s):

Schiff Base ◽

Molecular Docking ◽

Cell Lines ◽

Proliferative Activity ◽

Docking Study ◽

Reference Compound ◽

Molecular Docking Study ◽

Schiff Base Derivatives ◽

Hct 116 ◽

Mcf 7

Based on the use of s-triazine as a scaffold, we report here a new series of s-triazine Schiff base derivatives and their anti-proliferative activity against two cancer cell lines: human breast carcinoma (MCF-7), and colon cancer (HCT-116) compared with tamoxifen as a reference compound. Several derivatives exhibited growth inhibition activity in the sub-micromolar range. The results reveal that the s-triazine Schiff base derivatives showed varied activities and that the substituents on the s-triazine core have a great effect on the anti-proliferative activity. Compounds with a piperidino and benzylamino substituent on the s-triazine moiety 4b and 4c were most effective in both cell lines compared to the reference compound used. In addition, compound 4b has a para chlorine atom on the benzylidine residue, demonstrating the most potent activity with IC50 values of 3.29 and 3.64 µM in MCF-7 and HCT-116, respectively. These results indicate that in general, the nature of the substituents on the triazine core and the type of substituent on the benzilyldene ring significantly influenced the anti-proliferative activity. The results obtained from the anti-proliferative activity and the molecular docking study indicate that s-triazine-hydrazone derivatives may be an excellent scaffold for the development of new anti-cancer agents.

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