Addo Justice Kwaku, Owusu-Ansah Ernest, Dayie Nicholas T K D, Cheseto Xavier, Torto Baldwyn
Department of Chemistry, School of Physical Sciences, University of Cape Coast, Ghana.
International Centre of Insect Physiology and Ecology (icipe), P.O. Box 30772-00100, Nairobi, Kenya.
Heliyon. 2022 Oct 1;8(10):e10836. doi: 10.1016/j.heliyon.2022.e10836. eCollection 2022 Oct.
Thymol as a natural biological template can be modified chemically since the hydroxyl group makes it a candidate for structural modification. Thus, this study incorporated the triazole moiety on thymol and the chlorination of thymol moiety to help improve its biological potency.
A series of ten 1,2,3-triazole-thymol derivatives were synthesized from thymol, by a click reaction between O-propargyl terminal alkyne of thymol and its chlorothymol with benzyl azide and substituted benzyl azides. Their structures were confirmed by spectroscopic methods (H-NMR, C-NMR, IR, GC-MS-EI/CI and LC-ESI-QTOF-MS). The Well diffusion method using Müeller-Hinton agar plates was used to demonstrate the antimicrobial activities of the synthesized triazole-thymol derivatives on selected bacterial strains; 25922, ATCC25923, Methicillin resistant (MRSA), ATCC 29853, ESBL, NCTC 13438 and Meropenem Resistant
All the synthesized triazole-thymol derivatives showed significant but variable antibacterial activity against the seven medically important bacterial strains tested. The compound 4-((4-chloro-2-isopropyl-5-methylphenoxy)methyl)-1-(2-nitrobenzyl)-1-1,2,3triazole demonstrated a higher antibacterial activity with a mean zone of inhibition (38.7 mm) compared with ampicillin as the positive control which gave a zone size of 30.0 mm. In addition, the compound showed a three-fold potency than the parent compound, thymol (11.0 mm) against at a concentration of 100 μg/ml.
These results provide additional evidence of the exploitation of natural products like thymol as leads for drug development against medically important bacterial pathogens.
百里香酚作为一种天然生物模板，因其羟基使其成为结构修饰的候选对象，故可进行化学修饰。因此，本研究将三唑部分引入百里香酚，并对百里香酚部分进行氯化，以帮助提高其生物活性。
通过百里香酚的O-炔丙基末端炔烃与其氯代百里香酚与苄基叠氮化物及取代苄基叠氮化物之间的点击反应，从百里香酚合成了一系列十种1,2,3-三唑-百里香酚衍生物。通过光谱方法（氢核磁共振、碳核磁共振、红外光谱、气相色谱-质谱-电子轰击/化学电离和液相色谱-电喷雾-四极杆飞行时间质谱）确认了它们 的结构。使用穆勒-欣顿琼脂平板的平板扩散法来证明合成的三唑-百里香酚衍生物对选定细菌菌株的抗菌活性；25922、ATCC25923、耐甲氧西林（MRSA）、ATCC 29853、产超广谱β-内酰胺酶（ESBL）、NCTC 13438和耐美罗培南菌。
所有合成的三唑-百里香酚衍生物对所测试的七种医学上重要的细菌菌株均表现出显著但不同的抗菌活性。化合物4-((4-氯-2-异丙基-5-甲基苯氧基)甲基)-1-(2-硝基苄基)-1,2,3-三唑表现出较高的抗菌活性，平均抑菌圈为（38.7毫米），而作为阳性对照的氨苄西林的抑菌圈大小为30.0毫米。此外，该化合物在浓度为100微克/毫升时，对亲本化合物百里香酚（11.0毫米）的效力高出三倍。
这些结果为利用百里香酚等天然产物作为开发抗医学上重要细菌病原体药物的先导物提供了更多证据。
