Agrochemicals: A Brief Overview
Dongyou Liu in Handbook of Foodborne Diseases, 2018
Dithiocarbamates are a family of fungicides widely used since the 1940s to control fungal pathogens in a variety of crops. Compounds in this class include Maneb and Zineb (which include a metal moiety, manganese, and zinc, respectively) and Thiram (which does not have a metal moiety). These compounds have low acute toxicity, but chronic exposure is associated with adverse effects that may be due to the dithiocarbamate acid or the metal moiety. An important common metabolite of dithiocarbamates is ethylenethiourea, which is responsible for their effects on the thyroid (alterations of thyroid hormone levels, thyroid hypertrophy, and tumors) (110). Chronic exposure to Maneb has been associated with parkinsonism, possibly because of exposure to manganese, rather than the dithiocarbamate (111), and this fungicide has been recently withdrawn from the U.S. market (112). Interestingly, the structure of dithiocarbamate fungicides resembles that of disulfiram, an inhibitor of aldehyde dehydrogenase used in the treatment of alcoholism; for this reason, dithiocarbamates may interact with alcohol, leading to elevation in acetaldehyde levels (109). In addition, inhibition of aldehyde dehydrogenase, which also metabolizes DOPAL (3,4-dihydroxy phenyl acetaldehyde), a toxic metabolite of dopamine, is emerging as an important mechanism for a pesticidal etiology of Parkinson disease (113).
Role of Environmental Toxicants and Inflammation in Parkinson’s Disease
Abhai Kumar, Debasis Bagchi in Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Ziram (zinc dimethylbisdithiocarbamate), zineb (zinc ethylenebisdithiocarbamate), maneb (manganese ethylenebisdithiocarbamate), and other similar compounds are combined to form dithiocarbamates, which is widely used as fungicides. In animals, maneb induces specific neurodegeneration with dopaminergic influence. This interferes with mitochondrial activity, enhances oxidizing stress, and restricts proteasomal activity.169,170 Unlike MPP+, maneb prevents mitochondrial Complex III selectively. Ziram destroys dopaminergic neurons in culture by preventing the ubiquitin-proteasome system’s E1 ligase.171 Epidemiological research assessing concentrations of dithiocarbamate utilizing pesticide user details and spatial mapping observed an elevated incidence to PD correlated with zineb, ziram, and maneb.9,11 Together with toxicological data,172 these researches indicate possible synergy with paraquat.
New Biological Targets for the Treatment of Leishmaniasis
Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay in Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Three hitherto unexplored metal dithiocarbamates, namely maneb, zineb and propineb (Figure 14), demonstrated a strong anti-leishmanial activity on CA of L. major promastigotes, by inhibiting the parasite growth at sub-micromolar concentrations and in a dose-dependent fashion. Chemical structures of metal dithiocarbamate complexes (i.e., presented as monomeric units).
Design, synthesis and evaluation of quinolinone derivatives containing dithiocarbamate moiety as multifunctional AChE inhibitors for the treatment of Alzheimer’s disease
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Jie Fu, Fengqi Bao, Min Gu, Jing Liu, Zhipeng Zhang, Jiaoli Ding, Sai-Sai Xie, Jinsong Ding
The quinolinone scaffold is prevalent in a variety of pharmacologically active synthetic and natural compounds17. The reported biological activities of quinolinone derivatives including antioxidation, anti-osteoporosis, anti-influenza and anticancer activities, etc.18. Recent studies indicated that several quinolinone derivatives also presented potent AChE inhibitory activity, and molecular docking studies showed that the quinolinone moiety could bind to the PAS through a π-π stacking interaction19,20. Therefore, it can serve as a PAS binding moiety for design of dual binding site inhibitor. On the other hand, dithiocarbamate is a versatile pharmacophore, which has been receiving intense attention in recent years. Very recently, our group found that this moiety could interact with CAS of AChE, and many compounds possessing this moiety also displayed promising inhibitory activity for self-induced Aβ aggregation21,22. Meanwhile, unlike the benzyl piperidine of donepezil or tacrine that have been widely used as CAS binding group for design of multifunctional AChE inhibitors, the dithiocarbamate is still rarely used. Therefore, it is interesting to explore this scaffold as a CAS binding group to design multifunctional AChE inhibitors.
Discovery of orally active chalcones as histone lysine specific demethylase 1 inhibitors for the treatment of leukaemia
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Yang Li, Ying Sun, Yang Zhou, Xinyang Li, Huan Zhang, Guojun Zhang
The LSD1 inhibitory activity of all synthesised compounds C1∼C4 and D1∼D7 was examined according to reported references [24,27]. Their results of inhibitory activities against LSD1 in vitro were summarised in Table 1. In this work, Dithiocarbamate 26 and chalcone 4 were used as reference compounds. The replacement of the chlorine atom by the dithiocarbamate fragment resulted in a powerful improvement of LSD1 inhibitory activity for chalcone-dithiocarbamate derivatives D1∼D7 compared with the corresponding chalcone analogues (C1∼C4). Especially, compound D6 showed the potently inhibitory effect with an IC50 value of 0.14 μM (> 100-fold more potent than C3). This result suggests that dithiocarbamate moiety may play a synergistic role in determining activity.
Modulation of the airway smooth muscle phenotype in a murine asthma model and effects of nuclear factor-κB inhibition
Published in Journal of Asthma, 2019
Chen Qiu, Jie Li, Jian Zhang, Qi He, Lingwei Wang, Xuanwen Weng, Minjie Guan
On days 0 and 7, mice were sensitized by intraperitoneal injections of 20 ovalbumin (OVA, chicken egg albumin, grade V, Sigma, St. Louis, MO, USA) + 50 μl of Imject® Alum (Thermo Fisher Scientific, Boston, MA, USA) followed by daily 30-min 5% aerosol grade II OVA (Sigma, St. Louis, MO, USA) challenges for 5 consecutive days (acute model) or thrice weekly for 6 weeks (chronic model). Control groups were administered saline in the same manner. Mice were treated with pyrrolidine dithiocarbamate (PDTC, Sigma, St. Louis, MO, USA) or vehicle by i.p. injection 2 h before challenge with aerosolized OVA. The dosage (5 mg/kg) was determined based on a preliminary study and had the least side effects. Mice were analyzed 24 h after the last antigen challenge inhalation, and then the serum and lung tissues were harvested for further studies.
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