Khan Naqeeb Ullah, Sajid Muhammad, Obaidullah Ahmad J, Rehman Wajid, Faris Alotaibi Hadil, Bibi Saira, Alanazi Mohammed M
Department of Biochemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa 21300, Pakistan.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
ACS Omega. 2023 Jun 3;8(23):20767-20778. doi: 10.1021/acsomega.3c01378. eCollection 2023 Jun 13.
In humans, animals, and agriculture, parasitic nematode infection is a very serious issue. Many drugs are being used to control nematode infections. Owing to toxicity and nematodes' resistance to the available drugs, special attention is required to synthesize new drugs that are environmentally friendly with high-level efficacy. In the present study, various substituted thiazine derivatives (1 to 15) were synthesized, and the structures were confirmed by infrared, proton (H), and C NMR spectroscopies. The nematicidal potential of the synthesized derivatives was characterized using () as a model organism. Among all synthesized compounds, 13 (LD = 38.95 μg/mL) and 15 (LD = 38.21 μg/mL) were considered the most potent compounds. Most compounds showed excellent anti-egg-hatching activity. Fluorescence microscopy confirmed that compounds 4, 8, 9, 13, and 15 displayed a high apoptotic effect. The expressions of gst-4, hsp-4, hsp16.2, and gpdh-1 genes were high in affected (treated with thiazine derivatives) in comparison with normal . The present research revealed that modified compounds are highly effective as they showed the gene level changes in the selected nematode. Due to structural modification in thiazine analogues, the compounds showed various modes of action. The most effective thiazine derivatives could be excellent candidates for novel broad-scale nematicidal drugs.
在人类、动物和农业领域，寄生线虫感染是一个非常严重的问题。许多药物被用于控制线虫感染。由于现有药物的毒性以及线虫对这些药物的抗性，需要特别关注合成高效且环境友好的新药。在本研究中，合成了各种取代噻嗪衍生物（1至15），并通过红外光谱、质子（H）核磁共振光谱和碳（C）核磁共振光谱对其结构进行了确认。以（）作为模式生物对合成衍生物的杀线虫潜力进行了表征。在所有合成化合物中，13号（半数致死剂量LD = 38.95 μg/mL）和15号（LD = 38.21 μg/mL）被认为是最有效的化合物。大多数化合物表现出优异的抗卵孵化活性。荧光显微镜检查证实，化合物4、8、9、13和15具有较高的凋亡效应。与正常（）相比，受影响的（用噻嗪衍生物处理的）（）中gst-4、hsp-4、hsp16.2和gpdh-1基因的表达较高。本研究表明，修饰后的化合物具有高效性，因为它们在所选线虫中显示出基因水平的变化。由于噻嗪类似物的结构修饰，这些化合物表现出多种作用模式。最有效的噻嗪衍生物可能是新型广谱杀线虫药物的优秀候选者。
