Barbiturate- and Thiobarbituarte-Based s-Triazine Hydrazone Derivatives with Promising Antiproliferative Activities

Hessa Al Rasheed; Kholood Dahlous; Anamika Sharma; Essam Sholkamy; Ayman El-Faham; Beatriz G de la Torre; Fernando Albericio

doi:10.1021/acsomega.0c00468

Barbiturate- and Thiobarbituarte-Based s-Triazine Hydrazone Derivatives with Promising Antiproliferative Activities

ACS Omega. 2020 Jun 23;5(26):15805-15811. doi: 10.1021/acsomega.0c00468. eCollection 2020 Jul 7.

Authors

Hessa Al Rasheed¹, Kholood Dahlous¹, Anamika Sharma², Essam Sholkamy³, Ayman El-Faham^{1

4}, Beatriz G de la Torre⁵, Fernando Albericio^{1

2

6

7}

Affiliations

¹ Department of Chemistry, College of Science, King Saud University P.O. Box 2455, Riyadh 11451, Saudi Arabia.
² Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4000, South Africa.
³ Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁴ Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 12321, Egypt.
⁵ KRISP, College of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001, South Africa.
⁶ CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, and Department of Organic Chemistry, University of Barcelona, Barcelona 08028, Spain.
⁷ Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18-26, Barcelona 08034, Spain.

Abstract

A new class of compounds, which include s-triazine with pyrimidinetrione or thiopyrimidinedione moiety through a hydrazone linkage, were synthesized and characterized. The newly synthesized s-triazine hydrazone derivatives were evaluated in vitro against four cancer cell lines: A549, HepG2, HCT-116, and MCF-7. Several derivatives showed growth inhibition activity in the low microgram range. The results reveal that the barbiturate derivatives showed poor to no activity, while thiobarbiturate derivatives showed better activity than the analogues barbiturate derivatives. The substituents on the s-triazine moiety have a great effect on the antiproliferative activity, where derivatives with the piperidino and diethylamino on the s-triazine ring (5h) showed the highest activity against all of the tested cell lines (IC₅₀ 1.6 ± 0.6, 3.8 ± 0.3, 1.9 ± 0.4, and 1.2± 0.5 μg/mL for the tested cell lines A549, HepG2, HCT-116, and MCF-7, respectively). These results indicate that thiobarbiturates-s-triazine hydrazone derivatives may provide an excellent scaffold for the development of an anticancer drug candidate.