Synthesis and photochemical properties of psoralen derivatives

Abstract

A few psoralen derivatives $(Ps-O-C_3NH_2$, Ps-O-Glu, $Bis(C_4Ps)PIP$, $Bis(C_6Ps)PIP$, $Bis(C_8Ps)PIP)$ were synthesized and measured the photochemical and photobiological properties. The 5-substituent-8-methoxypsoralens $(-NO_2,-NH_2, -CH_2OH,-CHO,-CH_2OCH_3,-N(CH_3)_2,-Br)$ were synthesized to check the photophysical properties. All the experimental results were compared with those of 8-MOP which is widely used in clinics. The limiting factors in clinical use of photochemotherapeutic psoralens, 8-MOP, 5-MOP and TMP, are the poor water solubility and low intercalating efficiency with pyrimidine base pairs in DNA. Several psoralen derivatives $(Ps-O-C_3NH_2$, Ps-O-Glu, $Bis(C_4Ps)PIP$, $Bis(C_6Ps)PIP$, $Bis(C_8Ps)PIP)$, which are expected to have high reactivity and water solubility, were synthesized and investigated the solubility and photochemical inactivation of PCR by these compounds. $Ps-O-C_3NH_2$ and Ps-O-Glu have high water solubility than the widely used 8-MOP, however, these compounds did not prevent effectively the replication of DNA from PCR. The solubility of bispsoralen derivatives possessing two psoralens and one piperazine a molecule, 1,4-bis[n``-(8-psoralenoxy) alkyl] piperazine $(Bis(PsC_n)PIP n = 4,6,8)$ were comparable to that of 8-MOP but the piperazine-HCl salt formation of bispsoralens increased the solubility drastically. The relative binding constants of Bis(PsC_n)PIP (n = 4, 6, 8) to DNA were determined by the method of Hansen et al. The photo-crosslinking capacity of bispsoralens can be determined by using the non-renatured fraction (NRF). $Bis(PsC_n)$ PIP(n=4,6,8) shows the efficient intercalation into DNA, and good photo-crosslinking efficiency of DNA. $Bis(PsC_4)$PIP shows high lethality on bacteriophage T7 and can effectively inhibit the amplification of DNA by stopping the polymerase chain reactions in a short period of irradiation time. The order of hypochromism effect (% H) is in the order of Bis$(C_6Ps)PIP$ ≥ $Bis(C_4Ps P...