Electrostatic properties of some sulfur-containing radioprotectors

Abstract

Sulfur-containing molecules-and particularly the aminothiol class-are radioprotector agents. Electrostatic interactions occur between the cationic forms of these radioprotectors and the phosphate groups of DNA or the polar head of lecithin. Some electrostatic properties of four representative drugs were studied: cysteamine, methyl-2-cystearnine, WR 2578 dephosphorylated, and WR 1065. The conformations of these molecules are computed by using the PCILO method. Then the distribution of the cationic charge is specified with the help of the a6 initio method. The electrostatic potential resulting from the Mulliken atomic net charge distribution is also calculated. The electrostatic and conformational results are in good agreement with previous experimental studies from this laboratory. In the case of the interaction with DNA, these radioprotectors act as normal counterions whose interaction with DNA phosphate sites is discussed.

Conformation and electrostatic properties quantum determination of the new radioprotector and anticancer drug I-102

“…A previous investigation on cystearnine using contracted Clementi bases was described [13]. The results with STO 3G computation are very near those obtained previously with Clementi bases except the case of S I and HI atoms of sulfhydryl group; with contracted Clementi bases we have found for S, and HI: + O M and +0.15, respectively.…”

“…In fact, the active metabolite of WR-2721 is the WR-1065 free sulfhydryl form, which is able to interact with the nuclear material. Yuhas and coworkers have shown that WR-2721 is an anticancer molecule [6]; this drug can protect solid tumors and normal tissues, in a differential manner, in radiotherapy and chemotherapy and can also reduce the nephrotoxicity of cisplatin without antitumoral activity alteration [7-91. We have shown previously by spectrophotometric and dielectric measure- ments that a strong electrostatic interaction occurs between the cationic forms of these aminothiols and the phosphate sites of DNA [10-121. On the other hand, we have studied, using quantum computations, the conformations and electrostatic properties of cysteamine, methylated cysteamine, WR-2578 in free sulfhydryl form, and WR-1065 [5,[12][13][14].…”

“…On the other hand, we have studied, using quantum computations, the conformations and electrostatic properties of cysteamine, methylated cysteamine, WR-2578 in free sulfhydryl form, and WR-1065 [5,[12][13][14].…”