Organophosphorus Compounds as Chemical Warfare Agents: a Review

被引：232

作者：

Delfino, Reinaldo T. ^{[1
]}

Ribeiro, Tatiana S. ^{[1
]}

Figueroa-Villar, Jose D. ^{[1
]}

机构：

[1] Inst Mil Engn, Secao Engn Quim, BR-22290070 Rio De Janeiro, Brazil

来源：

JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY | 2009年 / 20卷 / 03期

关键词：

chemical warfare agents; organophosphorus compounds; acetylcholinesterase; oximes; neurotoxic agents; ACTIVE-SITE GORGE; DROSOPHILA-MELANOGASTER ACETYLCHOLINESTERASE; PHOSPHYLATED HUMAN ACETYLCHOLINESTERASE; SOMAN-INHIBITED CHOLINESTERASES; OXIMATE ALPHA-NUCLEOPHILES; PERIPHERAL ANIONIC SITE; PUSH-PULL MECHANISM; AB-INITIO QM/MM; IN-VITRO; CRYSTAL-STRUCTURES;

D O I：

10.1590/S0103-50532009000300003

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Chemical warfare agents constitute one of the greatest threats in the modern world. Among them, the neurotoxic agents are of special interest due to their high lethality and danger. Neurotoxic agents are organophosphorus compounds that act by inhibiting the enzyme acetylcholinesterase, which is fundamental for the control of transmission of nervous impulses. There are several ways of treating intoxication by organophosphorus compounds, but none of them is efficient against all the known neurotoxic agents or against all of their effects. This review focus on the use of organophosphorus compounds as neurotoxic chemical warfare agents. After a brief historical introduction, it will be done a discussion about the structural and biological characteristics of acetylcholinesterase, followed by a review of the properties of organophosphorus compounds and their application as chemical warfare agents. Finally, the ways of treatment against intoxication with these agents will be discussed, with emphasis on the oximes used for reactivating the inhibited acetylcholinesterase.

引用

页码：407 / 428

页数：22

共 177 条

[1] In vitro reactivation of sarin inhibited electric eel acetylcholinesterase by bis-pyridinium oximes bearing methoxy ether linkages [J].

Acharya, Jyotiranjan ;

Gupta, Arvind Kumar ;

Mazumder, Avik ;

Dubey, Devendra Kumar .

TOXICOLOGY IN VITRO, 2008, 22 (02) :525-530

[2] Inhibition of cholinesterases with cationic phosphonyl oximes highlights distinctive properties of the charged pyridine groups of quaternary oxime reactivators [J].

Ashani, Y ;

Bhattacharjee, AK ;

Leader, H ;

Saxena, A ;

Doctor, BP .

BIOCHEMICAL PHARMACOLOGY, 2003, 66 (02) :191-202

[3] AMINO-ACID-RESIDUES CONTROLLING REACTIVATION OF ORGANOPHOSPHONYL CONJUGATES OF ACETYLCHOLINESTERASE BY MONOQUATERNARY AND BISQUATERNARY OXIMES [J].

ASHANI, Y ;

RADIC, Z ;

TSIGELNY, I ;

VELLOM, DC ;

PICKERING, NA ;

QUINN, DM ;

DOCTOR, BP ;

TAYLOR, P .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (11) :6370-6380

[4]

AXELSEN PH, 1994, PROTEIN SCI, V3, P188

[5]

Bajgar J., 2004, J MED CHEM DEF, V1, P1

[6] Changes of acetylcholinesterase activity in different rat brain areas following intoxication with nerve agents: Biochemical and histochemical study [J].

Bajgar, Jiri ;

Hajek, Petr ;

Slizova, Dasa ;

Krs, Otakar ;

Fusek, Josef ;

Kuca, Kamil ;

Jun, Daniel ;

Bartosova, Lucie ;

Blaha, Vaclav .

CHEMICO-BIOLOGICAL INTERACTIONS, 2007, 165 (01) :14-21

[7]

Ballantyne B., 2007, Chemical Warfare Agents, P495, DOI [10.1002/9780470060032.ch25, DOI 10.1002/9780470060032.CH25]

[8] The aromatic "trapping" of the catalytic histidine is essential for efficient catalysis in acetylcholinesterase [J].

Barak, D ;

Kaplan, D ;

Ordentlich, A ;

Ariel, N ;

Velan, B ;

Shafferman, A .

BIOCHEMISTRY, 2002, 41 (26) :8245-8252

[9] Evidence for P-N bond scission in phosphoroamidate nerve agent adducts of human acetylcholinesterase [J].

Barak, D ;

Ordentlich, A ;

Kaplan, D ;

Barak, R ;

Mizrahi, D ;

Kronman, C ;

Segall, Y ;

Velan, B ;

Shafferman, A .

BIOCHEMISTRY, 2000, 39 (05) :1156-1161

[10] ORGANOPHOSPHATE AND CARBAMATE POISONING [J].

BARDIN, PG ;

VANEEDEN, SF ;

MOOLMAN, JA ;

FODEN, AP ;

JOUBERT, JR .

ARCHIVES OF INTERNAL MEDICINE, 1994, 154 (13) :1433-1441

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