Antitumor activity of novel N-sulfonylpyrimidine derivatives on the growth of anaplastic mammary carcinoma in vivo.
OBJECTIVE
The purpose of this study was to investigate in vivo antitumor activity of newly synthesized N-sulfonylpyrimidine derivatives 1-(p-toluenesulfonyl)cytosine (4H), 1-(p-toluenesulfonyl)cytosine hydrochloride (4HxHCl) and zinc(II) complex of 1-(p-toluenesulfonyl)cytosine (4K).


METHODS
In order to do that we have used mouse anaplastic mammary carcinoma (AMCa). Tumor cells (10(6)) in a volume of 0.02 ml were transplanted into the thigh of the right hind leg of CBA mice. All compounds were dissolved in distilled water immediately before injecting to animals.


RESULTS
Antitumor effect of these compounds depends on drug doses and time interval between tumor transplantation and drug application. Further the efficacy of these compounds depends on number of drug injections, i. e. whether drug was given in single or in multiple doses. Multiple doses of 400 mg/kg of 1-(p-toluenesulfonyl)cytosine (4H) showed good antitumor effect when applied on day 1, 3, 5, 7 and 9 after tumor transplantation. Still good but slightly lower antitumor effect was also achieved when that compound was given in a single dose (1,200 mg/kg) on day 1 after tumor transplantation. The longest period of tumor growth time was obtained after application of 1-(p-toluenesulfonyl)cytosine hydrochloride (4HxHCl) given as a single dose (300 mg/kg) on day 1 or on day 6 after tumor implantation. However, antitumor effect of zinc(II) complex of 1-(p-toluenesulfonyl)cytosine (4K) was very strong when 300 mg/kg was given on day 1 or day 6, while this effect was slightly lower when drug (200 mg/kg/inj) was given on day 1, 3, 5, 7 and 9 or on day 6, 8, 10, 12 and 14.


CONCLUSIONS
In this work it has been found that N-1-sulfonylcytosine derivatives have strong antitumor activity against mouse mammary carcinoma which is a good reason for further research of these compounds both in experimental and preclinical studies.
Pavlak
Marina
M
Department of Biology, Faculty of Veterinary Medicine, Zagreb University, Heinzelova 55, 10000, Zagreb, Croatia. marina.pavlak@vef.hr
Stojković
Ranko
R
Radacić-Aumiler
Matea
M
Kasnar-Samprec
Jelena
J
Jercić
Jure
J
Vlahović
Ksenija
K
Zinić
Biserka
B
Radacić
Marko
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000494:pharmacology*; D014105:Tosyl Compounds / Q000737:chemistry / Q000494:pharmacology*
C509985:(1-(4-toluenesulfonyl)cytosine)zinc(II); C509984:1-(4-toluenesulfonyl)cytosine; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D014105:Tosyl Compounds; D003596:Cytosine