Uma nova e eficiente síntese de oito derivados da classe 1,3,4-tiadiazolio-2-fenilaminas (1-8, sendo o derivado 8 inédito na literatura) foi realizada utilizando cloreto de tionila ou cloreto de trimetilsilano como catalisadores sob irradiação de microondas ou ultra-som. Os compostos alvos foram obtidos em bons rendimentos e em tempo extraordinariamente curtos, 5 min sob irradiação de microondas e 10 min sob irradiação de ultra-som, quando comparados com a metodologia tradicional (24 a 48 h em repouso a temperatura ambiente). Os melhores rendimentos foram obtidos usando irradiação de microondas e, de maneira geral, usando o cloreto de tionila ao invés de cloreto de trimetilsilano. A citotoxicidade foi avaliada frente à linhagem de leucemia humana K562 e do linfoma Daudi, apresentando resultados promissores para o derivado cloreto de 4-fenil-5-(4'-nitro-estiril)-1,3,4-tiadiazolio-2-fenilamina.A new and efficient synthesis of eight 1,3,4-thiadiazolium-2-phenylamine derivatives (1-8, where 8 is novel in the literature) was performed using thionyl chloride or trimethylsilyl chloride as catalysts under microwave or ultrasound irradiation. The target compounds were obtained in good yields and remarkably short times, 5 min under microwave irradiation and 10 min under ultrasound irradiation, where compared to traditional methodology (24 to 48 h at room temperature standing). The best yields were obtained using the microwave irradiation and, in general way, using thionyl chloride instead trimethylsilyl chloride. The cytotoxicity against K562 human leukemia and Daudi lymphoma lines was evaluated and showed promising results from the 4-phenyl-5-(4'-nitro-styryl)-1,3,4-thiadiazolium-2-phenylamine chloride derivative.Keywords: mesoionic heterocycle compounds, microwave, ultrasound, cytotoxic activity IntroductionMesoionic compounds are a special class of heterocycles with potential therapeutic applications due to their unique chemical properties. They possess a betaine-like character with a partial positive charge on the heterocyclic ring that is balanced by a negative charge located on an exocyclic atom or group.1,2 The large separation between the charged regions leads to large dipole moments of about 4-5 D.3,4 These properties suggest the possibility of interacting with biomolecules such as proteins and DNA. Additionally, the overall neutral character of these compounds enables them to cross biological membranes. Different classes of mesoionic compounds have demonstrated a wide range of biological activities such as anti-inflammatory and analgesic, 5 antiparasitic, 6,7 antibacterial, 8,9 antiplatelet, fibrinolytic, thrombolytic and broncholytic effects, 10 as well as anticancer potency.11-17 The promising therapeutic applications have led us to study these interesting compounds in our laboratory. We have previously described the survival enhancement of Ehrlich and Sarcoma 180 tumor-bearing mice treated with 4-phenyl-5-(4'-X-styryl)-1,3,5-thiadiazolium-2-phenylamine chlorides.12 Respiratory chain inhibition, transmembrane ...