Pentamidine

Pentamidine(MP-601205) is an antimicrobial agent.Target: AntiparasiticPentamidine has a potent in vitro antiprotozoal activity. Pentamidine displays cytotoxic activity against L. infantum promastigotes with IC50 of 2.5 μM. 2.5 μM Pentamidine induces early programmed cell death in 49.6% of L. infantum promastigotes. 2.5 μM Pentamidine induces a notorious decrease in promastigotes in both G1 and S phases relative to the control-untreated samples (G1:77.0 vs 15.0%; S:11.0 vs 2.4% for control- and pentamidine-treated promastigotes, resp). Pentamidine is able to bind with calf-thymus DNA (CT-DNA) and induces conformational changes in the DNA double helix. Pentamidine also binds with ubiquitin to modifiy the β-cluster of ubiquitin [1]. Pentamidine is an inhibitor of phosphatase of regenerating liver (PRLs). 1 μg/mL of Pentamidine complete inhibits the activity of recombinant PTP1B in dephosphorylating a phos-photyrosine peptide. 10 μg/mL of Pentamidine completely inhibits the activities of recombinant PRL-1, PRL-2 and PRL-3 in dephosphorylating a phosphotyrosine peptide substrate. Incubation with Pentamidine (1 μg/mL) for 48 h reduces the activity of intracellular PRL phosphatases in transfected NIH3T3 cells by more than 85%. 10 μg/mL Pentamidine completely inhibits the growth of melanoma cell line (WM9), prostate carcinoma cell line (DU145 and C4-2), ovarian carcinoma cell line (Hey), colon carcinoma cell line (WM480), and lung carcinoma cell line (A549) which all express endogenous PRLs [2].

Signaling Pathways >> Anti-infection >> Parasite

Research Areas >> Infection

[1]. Nguewa, P.A., et al., Pentamidine is an antiparasitic and apoptotic drug that selectively modifies ubiquitin. Chem Biodivers, 2005. 2(10): p. 1387-400.

[2]. Pathak, M.K., et al., Pentamidine is an inhibitor of PRL phosphatases with anticancer activity. Mol Cancer Ther, 2002. 1(14): p. 1255-64.

Hydroxychloroquine sulfate | Metronidazole | Emetine dihydrochloride hydrate | Ivermectin | Artemisinin | Levamisole (hydrochloride) | Fluralaner | RRx-001 | Avermectin | Quinidine | Bithionol | Flubendazole | Mebendazole | SQ109 | Artemether

DATA ITEMS CITED :

5

MOLECULAR FORMULA :

C19-H24-N4-O2

MOLECULAR WEIGHT :

340.47

WISWESSER LINE NOTATION :

MUYZR DO5OR DYZUM

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

28 mg/kg/1W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Nutritional and Gross Metabolic - body temperature increase

REFERENCE :

AIMDAP Archives of Internal Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1908- Volume(issue)/page/year: 145,2247,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

4 mg/kg/3D

TOXIC EFFECTS :

Behavioral - general anesthetic Behavioral - convulsions or effect on seizure threshold Nutritional and Gross Metabolic - body temperature increase

REFERENCE :

LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 246,338,1944

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

4 mg/kg

TOXIC EFFECTS :

Endocrine - hypoglycemia

REFERENCE :

AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 99,128,1983

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

50 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 18,794,1975

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Mammal - species unspecified

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

BSCFAS Bulletin de la Societe Chimique de France. (CDR-Centrale des Revues, 11, rue Gossin, F-92543 Montrouge Cedex, France) V.1- 1864- Volume(issue)/page/year: -,376,1968