Inhibition compounds

PSD. 1999. Methodology for the toxicological assessment of exposures from combinations of cholinesterase inhibiting compounds. Draft document. Medical and Toxicological Panel, Advisory Committee on Pesticides, Pesticides Safety Directorate, UK Ministry of Agriculture, Fisheries and Food, April 19,1999. 

Screening of microbial products has led to the discovery of a number of growth-inhibiting compounds that have proved to be clinically useful in cancer chemotherapy. Many of these antibiotics bind to DNA through intercalation between specific bases and block the synthesis of RNA, DNA, or both cause DNA strand scission and interfere with cell replication. All of the anticancer antibiotics now being used in clinical practice are products of various strains of the soil microbe Streptomyces. These include the anthracyclines, bleomycin, and mitomycin. 

For the highly inhibitive compounds in the TPA-induced inflammatory assay, we evaluated their antitumor-promoting activity by a standard initiation-promotion protocol [Fig. (3)] [37,40]. Initiation was achieved by a single application of 50 pg of DMBA (2), a well known tumor initiator, to the skin of backs of 8-week-old female ICR mice. From one week after initiation, 1 pg of TPA (1) was applied twice a week until week 20. The test compound (2.0 or 0.2 pM) dissolved in acetone-dimethyl sulfoxide (DMSO) (9 1, 100 pi) was applied 30 min before each TPA treatment. Groups of 15 mice were used. The number of tumors was counted weekly. 

Engineered variants of enzymes could be another approach in biosensor design for the discrimination and detection of various enzyme-inhibiting compounds when used in combination with chemometric data analysis using ANN. The crucial issues that should be addressed in the development of new analytical methods are the possibility of simultaneous and discriminative monitoring of several contaminants in a multi-component sample and the conversion of the biosensing systems to marketable devices suitable for large-scale environmental and food applications. 

The same conditions also resulted in the maximum glucose yield, 17.2 g/ 100 g of SFF. At the pretreatment conditions used, the formation of fermentation-inhibiting compounds was very low (results not shown) (16). The concentration of furfural in the slurry pretreated at 190°C for 10 min was about 0.3 g/L. No HMF was detected. 

To evaluate the degree of microbial growth inhibition caused by the hydrolysate used, Debaryomyces hansenii was grown in detoxified hydrolysates and in a hydrolysate only subjected to a pH correction, both nonsupple-mented and supplemented. As detoxification methods, anion-exchange resins and activated charcoal treatments were chosen because both enable the reduction of most of the fermentation-inhibiting compounds (7,38,39). 

Teasley, J.I. Identification of cholinesterase-inhibiting compounds from an industrial effluent. Environ. Sci. 

These devices are now being tested in demilitarization plants as monitors of stack exhaust atmospheres and work areas. We have not had the opportunity to determine the sensitivity of the devices to the numerous enzyme-inhibiting compounds which would be of interest to others. Generally, however, it is reasonable to expect, for instance, less sensitivity to P=S and P—S linkages and conversely better sensitivity to compounds where the sulfur is replaced by oxygen due to greater toxicity of these compounds. Such compounds as the carbamates, due to their inhibiting qualities, would also be expected to be detected with these systems. 

In another example, p-nitrophenyl chloroformate was required to introduce a sophisticated carbamate function in a multi-steps synthesis of retroviral protease inhibiting compounds (Ref. 26). The structure of the intermediate carbonate is given in scheme 30. 

Chen YH, Wang YH, Yu TH, et al. Transgenic zebrahsh line with over-expression of Hedgehog on the skin A useful tool to screen Hedgehog-inhibiting compounds. 

Symptoms of acute exposure to organophosphate or cholinesterase-inhibiting compounds may include the following numbness, tingling sensations, incoordination, headache, dizziness, tremor, nausea, abdominal cramps, sweating, blurred vision, difficulty breathing or respiratory depression, and slow heartbeat. Very high doses may result in unconsciousness, incontinence, and convulsions or fatality. 

In molecules D, the R side-chain was found to be critical for potency, but it could also dramatically influence the enzyme selectivity profile of the inhibition. Compounds D bearing large hydrophobic groups R (such as alkyl, cycloalkyl and arylalkyl groups) showed low-nanomolar, and even subnanomolar affinity for MMP-2, MMP-3, and MMP-13, and excellent selectivity against MMP-1. 

---