maneb and propineb

Dithiocarbamates have emerged as potent carbonic anhydrase (CA) inhibitors in recent years. Given that CAs are important players in cellular metabolism, the objective of this work was to exploit the CA-inhibitory property of dithiocarbamates as a chemotherapeutic weapon against the Leishmania parasite. We report here strong antileishmanial activity of three hitherto unexplored metal dithiocarbamates, maneb, zineb, and propineb. They inhibited CA activity in Leishmania major promastigotes at submicromolar concentrations and resulted in a dose-dependent inhibition of parasite growth. Treatment with maneb, zineb, and propineb caused morphological deformities of the parasite and Leishmania cell death with 50% lethal dose (LD50) values of 0.56 μM, 0.61 μM, and 0.27 μM, respectively. These compounds were even more effective against parasites growing in acidic medium, in which their LD50 values were severalfold lower. Intracellular acidosis leading to apoptotic and necrotic death of L. major promastigotes was found to be the basis of their leishmanicidal activity. Maneb, zineb, and propineb also efficiently reduced the intracellular parasite burden, suggesting that amastigote forms of the parasite are also susceptible to these metal dithiocarbamates. Interestingly, mammalian cells were unaffected by these compounds even at concentrations which are severalfold higher than their antileishmanial LD50s). Our data thus establish maneb, zineb, and propineb as a new class of antileishmanial compounds having broad therapeutic indices.

Topics: Animals; Antiprotozoal Agents; Apoptosis; Body Burden; Carbonic Anhydrase Inhibitors; Cell Line; Cell Survival; Leishmania major; Maneb; Mice; RNA, Protozoan; Thiocarbamates; Zineb

The determination of transition metal containing dithiocarbamate fungicides represents a challenging aspect of analytical object. They have a low stability, low solubility and stabilize versatile coordination monomers, dimers, disulfides and/or S-oxidized derivatives. Their diverse biological activities and agricultural implementation encompass plant prevention and crop protection against a variety of plants containing fungi and diseases of 400 pathogens and 70 cultures. Nonetheless, those dithiocarbamates (DTCs) are banned for agricultural use in Europe or have expiration at years 2016-2017 because of their highly toxic degradation products and/or metabolites, in particular ethylene thiourea; they found large-scale implementations in materials research and medicine. Despite the broad interdisciplinary of DTC application, due to the above reasons, they have received little attention in the rapidly growing field of analytical chemistry, and in particular, the analytical mass spectrometry. Therefore, the study reported on qualitative, quantitative and structural analysis of ten DTCs (1-10), using the matrix assisted laser desorption/ionization (UV-MALDI)-Orbitrap-mass spectrometry (MS) contributed considerably to the implementation of the method for environmental and foodstuffs monitoring. Its ultrahigh resolving power and capacity for direct solid-state analysis, at limited number of sample pretreatment steps, at concentration levels of analytes of up to femtogram per gram resulted to achievement of a highly precise analytical information for these non-trivial objects. The presented fully validated method and technique is based on the successful ionization of DTCs embedded in three novel organic salts (M1-M3). In this regard, the reported MS and the single-crystal X-ray diffraction data as well as the quantum chemical one are able to correlate the molecular structures in condense and in the gas phase. Despite the novelty of the fundamental methodological character of the research reported, the promising metrology contributed to the applied aspect of the UV-MALDI-MS as a robust analytical method for environmental and foodstuffs monitoring, which is tested on two commercially available crop protecting products such as Mancozeb® and Antracol®, respectively.

Topics: Environmental Monitoring; Europe; Fungicides, Industrial; Maneb; Mass Spectrometry; Metals; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thiocarbamates; Transition Elements; X-Ray Diffraction; Zineb

A gas chromatographic method with flame photometric detection (FPD (sulfur filter)) for analyzing the residues of 4 dithiocarbamates in 22 matrices in a heated closed vial has been established. The dithiocarbamate residues were decomposed to carbon disulfide (CS2) by SnCl2-HCl solution. The liberated CS2 was absorbed by hexane in the vial, and then determined by gas chromatography with FPD (sulfur filter). The results were expressed as the residues of dithiocabamates. The residue analysis method was validated by mancozeb, metiram, propineb and thiram in 22 matrices (apple, grape, etc). The average recovery ranges were from 72% to 110% with the relative standard deviations (RSD) between 0.8% and 22.0% when the fortified concentrations were between 0.06 and 3.0 mg/kg, and the quantitative analysis was performed by using external standard method. The limits of detection were in the range of 0.01-0.1 mg/kg (S/N = 3), and the limits of quantification were between 0.02 and 0.2 mg/kg (S/N = 10) for the 4 dithiocarbamate residues in the 22 matrices. This method is simple, fast, accurate, reproducible, and suitable for the determination of the 4 dithiocarbamate residues in the matrices mentioned in this paper.

Topics: Chromatography, Gas; Ditiocarb; Food Contamination; Fruit; Fungicides, Industrial; Maneb; Pesticide Residues; Thiocarbamates; Vegetables; Zineb

Dithiocarbamate propineb and maneb are organometal fungicides, which are widely used for the control of diseases in plants. Female Wistar rats were exposed orally to 200 and 400 ppm propineb (Zn-containing dithiocarbamate) and 250 ppm maneb (Mn-containing dithiocarbamate), from the 6th day of gestation up to birth. We found that the body weights of both newborn litters and their fungicide-treated mothers were lower than those of controls. Histological examination of the livers of fungicide-treated pregnant females and the offspring showed a variety of histopathological effects. Moreover, the analysis of Zn and Mn concentrations in the livers of pregnant females exposed to organometallic fungicides during pregnancy demonstrated that the metal concentrations in the liver were higher than those of controls. Similarly, the hepatic metal concentrations were significantly increased in the litters, indicating the transplacental passage of the organometallic fungicides.

Topics: Animals; Animals, Newborn; Female; Fungicides, Industrial; Histocytochemistry; Liver; Maneb; Manganese; Pregnancy; Pregnancy, Animal; Rats; Rats, Wistar; Zinc; Zineb

Dithiocarbamate propineb and maneb are organometal fungicides, which are widely used for the control of diseases in plants. Female Wistar rats were exposed orally to 200 and 400 ppm propineb and 250 ppm maneb, from the sixth day of gestation up to birth. We found that the body weights of both one-day old litters and their fungicide-treated mothers were lower than those of controls. Histological examination of the kidneys of fetus and fungicide-treated pregnant females showed a variety of histopathological effects. Moreover, the analysis of zinc (Zn) and manganese (Mn) concentrations (using inductively coupled plasma-atomic emission spectrometry) in the kidneys of pregnant females exposed to organometallic fungicides during pregnancy demonstrated that the metal concentrations in the kidney were higher than those of controls. However, the renal metal concentrations were significantly increased in the litters subjected to the fungicides during gestation, indicating that high levels of the trace metals in the organ of fetus may well be due to the fungicides easily passing the placental barrier.

Topics: Animals; Animals, Newborn; Body Weight; Female; Fetus; Fungicides, Industrial; Kidney; Male; Maneb; Manganese; Maternal-Fetal Exchange; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Zinc; Zineb

Oral administration of high dosages of the dithiocarbamate pesticides maneb and mancozeb was teratogenic in rats but not in mice. The malformations, severe limb and craniofacial defects, were pronounced after maneb treatment but less so after mancozeb and propineb, zinc-containing compounds. The teratogenic effect of maneb was progressively reduced by simultaneously administering increasing amounts of zinc acetate. The mechanism of the teratogenic effect may involve the compounds being chelating agents, trapping zinc required for many important enzyme systems.

Topics: Abnormalities, Drug-Induced; Acetates; Animals; Female; Fetal Resorption; Maneb; Mice; Pregnancy; Rats; Thiocarbamates; Zinc; Zineb