Al-Omary Fatmah A M, Alvarez Natalia, Al-Rasheed Lamees S, Veiga Nicolás, Hassan Hanan M, El-Emam Ali A
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Química Inorgánica, Facultad de Química, Universidad de la República, Av. General Flores 2124, Montevideo 11800, Uruguay.
ACS Omega. 2023 Mar 30;8(14):13465-13477. doi: 10.1021/acsomega.3c01469. eCollection 2023 Apr 11.
In this study, two adamantane-linked isothiourea derivatives containing a common 4-chlorophenyl substituent coupled with 4-nitrobenzyl or 4-bromobenzyl moieties were synthesized. Both derivatives were characterized, in the solid state and in solution, through a synergistic combination of experimental and in silico techniques, and the results are of great value for the chemical and structural characterization of related compounds. The crystal structures of both derivatives were analyzed in depth, including Hirshfeld surface analysis and lattice energy calculations, revealing a predominant dispersive component of the total energy that stabilizes crystal packing. Both compounds showed potent broad-spectrum antibacterial activity and moderate activity against the pathogenic fungus . In addition, in vitro anti-proliferative activity assays showed that the 4-bromobenzyl analogue displays higher activity than the 4-nitrobenzyl one, with IC values under 30 μM against five human cancer cell lines. Our results give evidence of the potential of the adamantane/isothiourea combination to render auspicious scaffolds for new potential chemotherapeutic agents.
在本研究中，合成了两种含有常见4-氯苯基取代基并与4-硝基苄基或4-溴苄基部分相连的金刚烷连接的异硫脲衍生物。通过实验技术和计算机模拟技术的协同结合，对这两种衍生物在固态和溶液状态下进行了表征，其结果对于相关化合物的化学和结构表征具有重要价值。对这两种衍生物的晶体结构进行了深入分析，包括 Hirshfeld 表面分析和晶格能计算，结果表明总能量中占主导的色散成分稳定了晶体堆积。这两种化合物均表现出强效的广谱抗菌活性以及对致病真菌的中等活性。此外，体外抗增殖活性测定表明，4-溴苄基类似物比4-硝基苄基类似物表现出更高的活性，对五种人类癌细胞系的IC值低于30 μM。我们的结果证明了金刚烷/异硫脲组合为新型潜在化疗药物提供良好支架的潜力。
