590 Biological and in-silico characterization of pyrazole and pyrazolone derivatives: Identifies novel anti-skin cancer, antioxidant and tyrosinase inhibitory agents

The psychosocial burden akin to cutaneous conditions such as cancer and hyperpigmentation disorders, make their management very sensitive. Current therapeutic interventions, are associated with side-effects, cost, invasiveness bioavailability issues. Herein, 26 new pyrazole pyrazolone compounds were synthesized via microwave-assisted reactions pharmacokinetic parameters ADMET predicted by in-silico methods. In addition, these evaluated for anti-proliferative, antioxidant, anti-tyrosinase effects. Many potent hits identified low-micromolar IC50 values against non-melanoma cells A431 SCC-12 (p<0.001), melanoma SKMel-28 A375 (p<0.01) several-fold affinity over control (HaCaT) than Cisplatin, a known anticancer drug. most hit significantly reduced scratch wound healing colony formation induced apoptosis evidence modulation of cleaved caspase 3, 9, PARP levels Bax/Bcl-2 ratio (p<0.01). Tyrosinase inhibition assay nine effective derivatives up 98% compared the Arbutin 58% (p<0.001). Using antioxidant assay, six active superior scavenging activity quercetin (p<0.01), but comparable ascorbic acid identified. Employing Swiss Target Prediction SwissADME databases, several good binding affinities targets COX-1/2, FLT3, VEGFRI, MAPK-4, JAK-1 identified, which also exhibited excellent intestinal, oral topical absorption properties. summary, novel promising anti-cancer, anti-oxidant tyrosinase inhibitory warrant further characterization investigation in skin disorders.