Synthesis And Antitumor Activity Of Chromano[4,3-d]-△～(1,9b)-1,2,3-thiadiazolines And Its Analogue

Flavonoids, such as apigenin, baicalein, genistein, flavopiridol, quercetin genistein and flavopiridol have antitumor activity. These compounds are cytotoxic to cancer cells but have no or insignificant activity in normal cells. These beneficial properties prompted synthesis of flavonoid derivatives.For many years, 1,2,3-thiadiazole derivatives were reported for their bioactivity including antitumor and antibacterial. It was thought the combination of the flavonoid with the 1,2,3-thiadiazole may be benefit to the biological activity. Thus, the title compounds were synthesized with the hope that they might be having antitumor activity.1-aryl-4-aryl-chromano[4,3-d]-Δ^1,9b-1,2,3-thiadiazolines were synthesized with flavanone-4-arylhydrazone in SOCl₂ then the reaction mixture was treated with alcohol. In all the products, position 3a- and 4- were substituted by alkyloxy- and position 2"- was substituted by Cl. Some of products were substituted by chlorine on A ring and B ring, the number and position of which depending on the substituent of material. By this method, 25 compounds were prepared.4-aryl-chromene [4, 3-d]-1,2,3-thiadiazoles were prepared with flavanone-4-semicarbazone in SOCl₂ and then in EtOH. The result showed that position 4- of some products was substituted by Cl. The conceivable mechanism was proposed to explain their formation. 11 compounds were prepared by the same method.All the structures were confirmed by ¹HNMR and IR, and some of them also confirmed by MS. The structure of 6a was determined by single crystal X-ray crystallography, and also confirmed by ¹³CNMR, ¹H-¹H COSY, HMQC.All the thiadiazolines prepared in this study were tested for their cytotoxicity against HL-60. At the concentration of 5mg/L, most of the compounds showed some activity in inhibition proliferation. The cytotoxic data showed that 9 compounds displayed strong activity against HL-60 (IC₅₀ < 1μM). Among them, compound 7b,showed the most potent activity (IC5o=O.14uM).The low solubility of all the compounds, especially the 4-aryl-chromene [4,3-d]-l,2,3-thiadiazoles, blocked their pharmacological study.