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

In humans, animals,and agriculture, parasitic nematodeinfectionis a very serious issue. Many drugs are being used to control nematodeinfections. Owing to toxicity and nematodes' resistance tothe available drugs, special attention is required to synthesize newdrugs that are environmentally friendly with high-level efficacy.In the present study, various substituted thiazine derivatives (1to 15) were synthesized, and the structures were confirmed by infrared,proton (H-1), and C-13 NMR spectroscopies. Thenematicidal potential of the synthesized derivatives was characterizedusing Caenorhabditis elegans (C. elegans) as a model organism. Among all synthesizedcompounds, 13 (LD50 = 38.95 mu g/mL) and 15 (LD50 = 38.21 mu g/mL) were considered the most potent compounds.Most compounds showed excellent anti-egg-hatching activity. Fluorescencemicroscopy confirmed that compounds 4, 8, 9, 13, and 15 displayeda 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 modifiedcompounds are highly effective as they showed the gene level changesin the selected nematode. Due to structural modification in thiazineanalogues, the compounds showed various modes of action. The mosteffective thiazine derivatives could be excellent candidates for novelbroad-scale nematicidal drugs.