There is a need to control Spodoptera frugiperda with new pesticides that have unusual modes of action. Spodoptera frugiperda initial larval instars can spin silk threads which would be the target of synthetic 2-Cyano-N-(3-(N-(thiazol-2-yl) sulfamoyl) phenyl) acetamide. The toxicity of synthetic derivatives (Ar1, Ar2, and Ar3) was tested against 1st and 2nd larval instars. Besides, the silk spinning ratio was examined after treatments with LC50s of certain derivatives, and different shapes of produced silk were detected in comparison with the control by SEM. In addition, malformation percentages of initial instars and latent effects were recorded. Biochemical experiments were done upon treatments with LC50s of derivatives. Results showed that Ar1 was the most effective derivative against S.frugiperda 1st and 2nd larval instars with LC50 values of 781.65 and 904.39 µLL¯¹, respectively. Spinning ratios were 6.67,13.33,26.67 and 93.33 % for Ar1, Ar2, Ar3, and control, respectively, and differences in silk strands were detected morphologically upon potent interaction with the induced treatments. Results were explained upon more biochemical analysis which showed that Ar1 recorded the highest values of total protein and total lipids, while it was the lowest in the case of enzymes such as protease, amylase, and Na+K+ATPase. It could be concluded that synthetic 2-Cyano-N-(3-(N-(thiazol-2-yl) sulfamoyl) phenyl) acetamide derivatives would be used as promising insecticides and anti-spinning silk threads compounds effectively against Spodoptera frugiperda larvae with registered high mortality percentages.