Synthesis and modification of novel thiazole-fused quinoxalines as new insecticidal agents against the cotton leafworm Spodoptera litura: design, characterization, in vivo bio-evaluation, toxicological effectiveness, and study their mode of action

Abstract

Herein, novel thiazolo[4,5-b]quinoxalin-2-ones 2–6 and thiazolo[4,5-b]quinoxalin-2(3H)-imines 7–9 were synthesized and characterized using elemental analysis, IR spectroscopy, and ¹H/¹³C NMR to confirm their structures. The efficacy of the newly designed thiazolo-quinoxalines 2, 3, 4, 5, 7, 8, and 9 against the cotton leafworm S. litura (2nd and 4th instar larvae) was evaluated, and results revealed insecticidal activity with variable and good mortality percentages. A SAR study was also discussed. Additionally, compound 3 exhibited the highest insecticidal activity, with mortality% values ranging from 86% ± 7.21% to 97% ± 1.52% and from 66.00% ± 6.24% to 86.33% ± 6.90% at concentrations of 625–2500 mg L⁻¹ against the 2nd and 4th instar larvae, respectively. The probit analysis revealed that the thiazolo[4,5-b]quinoxalin-2(3H)-one derivative 3, after 5 days of treatment, exhibited LC₅₀ values of 141.02 and 366.73 mg L⁻¹ for the 2nd and 4th instar larvae, respectively. The LT₅₀ values ranged from 0.52 to 1.92 days for the 2nd larval instar and from 1.95 to 2.47 days for the 4th larval instar. The corresponding toxicity index (TI) values were 86.21% for the 2nd instar and 78.47% for the 4th instar larvae. The mode of action of compound 3 was assessed through physiological, histological, and SEM analyses on the 4th larval instar. The physiological bioassay revealed a significant increase in total carbohydrate and protein levels compared to the control group. However, the enzymatic study showed a significant decrease (P < 0.05) in the levels of aspartate aminotransferase (AST/GOT), alanine aminotransferase (ALT/GPT), and alkaline phosphatase (AlP), while acetylcholinesterase (AChE) levels significantly increased. SEM analysis revealed malformations in the external body, while histological examination demonstrated severe damage to the gut epithelium and regenerative cells in the midgut tissues.