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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Valiveti, Aditya Kapil Bhalerao, Uma M. Acharya, Jyotiranjan Karade, Hitendra N. Gundapu, Raviraju Halve, Anand K. Kaushik, Mahabir Parshad |
| Description | Country affiliation: India Author Affiliation: Valiveti AK ( Process Technology Development Division, Defence Research & Development Establishment, Jhansi road, Gwalior 474 002, India.); Bhalerao UM ( Process Technology Development Division, Defence Research & Development Establishment, Jhansi road, Gwalior 474 002, India.); Acharya J ( Process Technology Development Division, Defence Research & Development Establishment, Jhansi road, Gwalior 474 002, India. Electronic address: jracharya@rediffmail.com.); Karade HN ( Process Technology Development Division, Defence Research & Development Establishment, Jhansi road, Gwalior 474 002, India.); Gundapu R ( Process Technology Development Division, Defence Research & Development Establishment, Jhansi road, Gwalior 474 002, India.); Halve AK ( School of Studies in Chemistry, Jiwaji University, Gwalior, India.); Kaushik MP ( Process Technology Development Division, Defence Research & Development Establishment, Jhansi road, Gwalior 474 002, India.) |
| Abstract | A series of mono pyridinium oximes linked with arenylacetamides as side chains were synthesized and their in vitro reactivation potential was evaluated against human acetylcholinesterase (hAChE) inhibited by organophosphorus inhibitors (OP) such as sarin, VX and tabun. The reactivation data of the synthesized compounds were compared with those obtained with standard reactivators such as 2-PAM and obidoxime. The dissociation constant (KD) and specific reactivity (kr) of the oximes were also determined by performing reactivation kinetics against OP inhibited hAChE. Among the synthesized compounds, oximes 1-(2-(4-cyanophenylamino)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium chloride (12a) and 4-((hydroxyimino)methyl)-1-(2-(4-methoxyphenylamino)-2-oxoethyl)pyridinium chloride (2a) were found most potent reactivators for hAChE inhibited by sarin. In case of VX inhibited hAChE majority of the oximes have shown good reactivation efficacies. Among these oximes 1-(2-(benzylamino)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium chloride (18a), 4-((hydroxyimino)methyl)-1-(2-(4-(methoxycarbonyl)phenylamino)-2-oxoethyl)pyridinium-chloride (14a) and 12a were found to surpass the reactivation potential of 2-PAM and obidoxime. However, the synthesized oximes showed marginal reactivation efficacies in case of tabun inhibited hAChE. The pKa value of the oximes were determined and correlated with their observed reactivation potential. |
| File Format | HTM / HTML |
| ISSN | 00092797 |
| Volume Number | 237 |
| e-ISSN | 18727786 |
| Journal | Chemico-Biological Interactions |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2015-07-25 |
| Publisher Place | Ireland |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Biochemistry Discipline Pharmacology Acetylcholinesterase Drug Effects Cholinesterase Reactivators Chemical Synthesis Organophosphorus Compounds Pharmacology Oximes Pyridinium Compounds Humans In Vitro Techniques Kinetics Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Toxicology |
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