Explanation of the mechanism of carcinogenesis and syntheses of anticancer agents with high selectivity

摘要: In 1979, the mechanism of chemical carcinogenesis, a challenging and difficult scientific problem pending for number years, was explained by Dai Qianhuan. The named di-region theory predicted that carcinogen always metabolizes to form special bi-functional alkylating agent. This agent induces cross-linkages between complementary base pairs in DNA switches on initial mutageneses genomes including point frameshift mutations. This, turn, further deep production various chimeric chromosomes, deletions other aberrations found genomes. end this initiates carcinogenesis whole cell through reverse transcription after lengthy incubation period. Recently, laboratory has verified physical oncogenesis induced radiation asbestos as well endogenous factors such estrogen or diethyl-stilbestrol switch inducing formation DNA. Di-region now been supported many experimental observations mutational spectra carcinogens. potential teratogenesis, sterility mutagenesis lumped together genetic toxicity appears originate almost uniformly from cross-linking bases, i.e. malignant cross-linking, which is accordance with theory. Other forms non-complementary benign cross-linkings, show alkylation anticancer activity but lack toxicity. predictable design synthesis high selectivity efficacy low toxicity, goal long pursued cancer chemotherapy, have realized first time inhibiting heightening using principles A series patented new platinum complexes called di-regioplatins, based above predetermined design, reported. these kill rates, tumor-inhibition rates ultimate life-span two mouse carcinoma models several com-pounds cis-di-substituted-benzylaminodihaloplatinum (II) are notably higher than those cisplatin, their toxicities all much lower cisplatin. Based predictive group theory, complex, cis-diammine-cyclopentane-1,1-dicarboxylato-platinum minoplatin, synthesized making minimal structural revision adding an CH2 unit four-member ring carboplatin. water solubility minoplatin double carboplatin, yet its lipid Animal acute only half curative effect rapid growing animal tumor model ascites-type remarkably Genetic measured TA 102 strain 1/200 cisplatin 1/10 Minoplatin, opposed shows no teratogenesis offspring pregnant female mice. Additionally, some recent empirical research results comments perspective predicting agents presented. We anticipate future clinical testing will demonstrate di-regioplatins examples class consisting highly selective, tailored second generation agents.