Toxicity and structure–activity relationship of vanadium(IV) acetophenone–isoniazid hydrazone complexes in brine shrimp (Artemia salina) with in vivo cross-model comparison
Abstract The toxicity of vanadium(IV) acetophenone–isoniazid hydrazone complexes (V1–V4) was evaluated in Artemia salina. Nauplii were exposed for 24–72 h at 1, 5, 10, and 50 mg/L. Responses were concentration dependent: reduced hatching, increased mortality, and morphological changes (appendage and carapace defects, intestinal accumulation). Toxicity ranked by substituent: V2 (F) most toxic (≈60% mortality at 72 h, 50 mg/L), V3 (Cl) intermediate, V1 (H) and V4 (Br) lower (near 30% under the same conditions). Findings were compared with data from streptozotocin-induced diabetic Wistar rats. V4, moderately toxic in Artemia, showed the strongest antihyperglycemic effect (ca. 72% glucose reduction to near-normoglycemia) and the lowest renal bioaccumulation. V2 aligned with unfavorable renal/hepatic markers. V1 was well tolerated in Artemia and produced moderate glucose lowering with lipid improvements. V3 gave intermediate efficacy but higher bioaccumulation and hematological deviations. A. salina is a suitable early toxicity screen that, combined with mammalian data, reveals structure–activity–toxicity relationships. Halogen substitution modulates both efficacy and toxicity: Br provides the most balanced profile, F the highest liability, and H the safest but least potent. V4 (Br) emerges as the leading candidate for further preclinical study. Graphical abstract