Synthesis, X-Ray Crystal Structures, and Preliminary Antiproliferative Activities of New s-Triazine-hydroxybenzylidene Hydrazone Derivatives

Assem Barakat,Hessa H Al-Rasheed,Abdullah Mohammed Al-Majid,Farid A Badria,Fardous F El-Senduny,Ayman El-Faham,Zainab Almarhoon,Hazem A Ghabbour

doi:10.1155/2019/9403908

Assem Barakat, Hessa H Al-Rasheed + Show 6 more

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https://doi.org/10.1155/2019/9403908

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Abstract

We herein report a new small library of Schiff-base compounds that encompasses s-triazine and (2 or 4)-hydroxylbenzylidene derivatives. These compounds were synthesized through a hydrazone linkage connecting both the s-triazine and hydroxybenzylidene derivatives. The synthetic strategy adopted allowed the synthesis of the target compounds with excellent yields and purities as observed from their NMR (1H and 13C) and elemental analysis. Furthermore, 4f, 5b, and 5f were further confirmed by X-ray single crystal diffraction technique. The preliminary antiproliferative activities for the synthesized compounds were tested against two different cancer cell lines including breast cancer (MCF-7) and colon cancer (HCT-116). From the eighteen compounds, which have been examined, only two derivatives having piperidine moiety showed more selectivity against the two cell lines MCF-7 and HCT-116, while the others showed very weak activity. The position of the hydroxyl group in the benzylidine ring and the substituent on the s-triazine moiety has great effect on the activity of the prepared compounds. The IC50 values for the two derivatives 4a and 5a evaluated against breast cancer cells, very close to those for the chemotherapeutic drug cisplatin, are 27 µM (13.3 µg/mL), 17 µM (8.4 µg/mL), and 20 µM (6 µg/mL) for 4a, 5a, and cisplatin, respectively. These results propose the preliminary antiproliferative activity of these two derivatives may deserve further consideration for development of new derivatives as potent anticancer agents.

Highlights

Schiff bases have gained great importance in which these compounds have been found to exhibit antimicrobial [1,2,3,4], antiviral [1, 5], antioxidant [6], and antitumor [7, 8] activities. ese activities are largely attributed due to the presence of the azomethine (R-NH-N C-R) group which is important synthon for several transformations [9, 10]
The hydrazone linkage provides an appropriate system for pH-dependent of drugs release [11]
Cyanuric chloride has been used as building blocks in the Journal of Chemistry synthesis of vast derivatives bearing the s-triazine moiety, due to the low-cost, commercial availability, and ease of displacement of the three chlorine atoms by various nucleophiles under controlled temperature [24]. ese advantages allowed for the preparation of mono, di- and trisubstituted s-triazines derivatives with a wide range of biological activities [25,26,27], such as adenosine receptor antagonist [28], antiamoebic [29], antileishmanial [31,32,33], anticancer [32], antimalarial [34], antimicrobial [35,36,37], antiviral [38], antitubercular [39], carbonic anhydrase inhibitor [40], and cathepsin B inhibitor [41], Previously, we reported new series of s-triazine Schiff-base derivatives [42,43,44]; among of the reported compounds, only three derivatives were able to inhibit the growth of lung (A549) and hepatocellular carcinoma (HepG2) cancer cell lines

Summary

Introduction

Schiff bases have gained great importance in which these compounds have been found to exhibit antimicrobial [1,2,3,4], antiviral [1, 5], antioxidant [6], and antitumor [7, 8] activities. ese activities are largely attributed due to the presence of the azomethine (R-NH-N C-R) group which is important synthon for several transformations [9, 10]. E results showed that s-triazine with the two substituents methoxy and piperidine in the target product made the compound more selective to the hepatocyte carcinoma HepG2 (IC50 value of 1.5 μg/mL).

Results

Conclusion