N-(4-CHLOROPHENYL)-N'-(ISOPROPYL)-IMIDODICARBONIMIDIC DIAMIDE

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Product Introduction:
Proguanil is a precursor drug of antimalarial drugs that metabolizes to the active metabolite cycloguanosine. Cycloguanosine is a dihydrofolate reductase (DHFR) inhibitor.
Related categories
Signal Pathways>>Anti infection>>Parasites
Research Fields>>Infection
In vitro studies have shown that Proguanil itself only exhibits weak antimalarial activity in vitro (IC50=2.4-19 μ M) Its effectiveness depends on the active metabolite cycloguanil (IC50=0.5-2.5nM). Cycloguanidine is an inhibitor of dihydrofolate reductase (DHFR). The combination of atovaquone and chloroguanidine is synergistic in vitro. Both drugs have activity on the gametophyte cells and the pre erythrocytic (liver) stage of malaria parasites [1]. Proguanil is used as a biguanide instead of its metabolite cycloguanil (a parasite dihydrofolate reductase [DHFR] inhibitor) to enhance the atovaquone effect; Due to the fact that the effects of other mitochondrial electron transport inhibitors, such as thiazole and antibiotics, are not altered by the presence of chloroguanidine, the enhancement mediated by chloroguanidine has specificity for atovaquone [2]. Chloroguanidine, metabolite 4-chlorophenyl-1-biguanidine (CPB), and active metabolite cycloguanidine (CG) reversibly inhibit the 5-HT3 receptor reaction, with IC50 values of 1.8,1.48 and 4.36, respectively μ M [3].
In vivo research on Proguanil can induce infertility in rats, which may play a role by distorting the blood-testis barrier formed by Sertoli cells. The duration dependence significantly reduces body and organ weight as well as sperm parameters. The serum testosterone levels of rats treated with chloroguanidine were significantly reduced [4]. Provide Malarone (atovaquone and chloroguanidine) for experimental study B Two dogs infected with gibsoni in the chronic phase and three dogs in the acute phase resulted in a decrease in parasitemia and clinical improvement was observed [5].
Cell experiments were conducted to culture supporting cells obtained from rats aged 16 to 18 days, and 0.3 μ M to 10 μ M was treated with chloroguanidine for 5 days, followed by measurement of supporting cell viability and nuclear integrity. In addition, evaluate the genetic expression of transferrin and glial cell derived neurotrophic factor [4].
Animal experiment rats: The 10 to 12 week group of rats were administered chloroguanidine (2.9mg/kg body weight) daily for 5 days and 6 weeks, respectively. Afterwards, body weight and reproductive organ weight were taken, sperm parameters were analyzed, and histological examinations of the testes and epididymis were performed. In addition, determine serum testosterone, luteinizing hormone, and follicle stimulating hormone levels