Nematicidal Characterization of Newly Synthesized Thiazine Derivatives Using Caenorhabditis elegans as the Model Organism

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 (1H), and 13C NMR spectroscopies. The nematicidal potential of the synthesized derivatives was characterized using Caenorhabditis elegans (C. elegans) as a model organism. Among all synthesized compounds, 13 (LD50 = 38.95 μg/mL) and 15 (LD50 = 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) C. elegans in comparison with normal C. elegans. 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.