Synthesis And Biological Activity Studies Of Benzophenone Hydrazone And Podophyllotoxin Thiourea Derivatives

Due to a wide range of biological activities, thiourea compounds have attracted people's attention since the 1950s which are primarily used in the pesticide fields, such as weeding, insecticidal, acaricidal, plant growth regulators. Nuvanol (insecticide), Thiosemicarbazide (fungicides), Diafenthiuron (acaricides), Guanyl thiourea (nitrogen increased agonist) and Fuphenthiourea (plant growth regulator) are typical thiourea compounds. Comparing with other pesticides, thiourea compounds show numerous advantages including small injury, less residue and environmental friendliness. Thiourea compounds are also used in medicinal field with fungicides, anti-HIV, anti-TB, anti-tumor activities. Nowdays, there have been numerous thiourea medicines on the market, such as S-(2-aminorthyl) isothiouronium (neural cell generating drug), Propylthiouracil (antithyroid drug), Carbimazole (antithyroid). In view of thiourea compounds are widely used in pesticides and medicinal fields, introducing thiourea structure to benzophenone hydrazone and podophyllotoxin maybe develop their bioactivities through splicing of the chemical active structure. Detail studies are as follows:1. Design, synthesis and bioactivity evaluation of N-substituted-[(4-chlorophenyl) (4-trifluoromethyl-sulfonylphenyl)-ketone] thiosemicarbazone.By introducing thiourea structure to benzophenone hydrazone through the reaction of isothiocyanate wih the amino, we synthesize a series of N-substituted-[(4-chlorophenyl) (4-trifluoromethyl-sulfonylphenyl)-ketone]thiosemicarbazone. In order to complete structure-function relationship, urea group is also introduced to benzophenone hydrazone to obtain a series of N-substituted-[(4-chlorophenyl) (4-trifluoro-methyl-sulfonylphenyl)-ketone] semicarbazone. All of synthesized compounds are evaluated for their acaricidal activities against T. Cinnabarinus and the insecticidal activity against B. brassicae (Linnaeus). The results show that the introduction of thiourea and urea groups could significantly improved the pesticides activity of benzophenone hydrazone, acaricidal activity is particularly obvious.2. Design, synthesis and potent cytotoxic activity of 4?-(3"-substituted formyl-thioureido)-4-deoxypodophyllotoxin 4?-amino-4-desoxypodophyllotoxin is obtained by simplely modified from podophyllotoxin, which is coupled with the appropriate acylisothiocyanates to provide a series of acyl thiourea derivatives. In order to increase diversity, five 4'-demethylepipodophyllotoxin derivatives are also synthesized through similar way. These new acyl thiourea derivatives of podophyllotoxin and 4'-demethyl-epipodophyllotoxin are screened for their cytotoxicity against four human tumor cell lines, including human lung adenocarcinoma cells (A549), human prostate cancer cells (DU-145), human oral epidermoid cancer cells (KB) and human oral epidermoid cancer cells drug-resistant strains of cells (KBvin). The results show that the introduction of the acyl thiourea group obviously improves the antitumor activity against KBvin, A549, DU-145, and KB. Among them, the derivatives 13b,13c and the 13o exhibite the best anti-tumor activity, whose antitumor activities are all more than 20 times of etoposide.