Abstract
Interest in nitroheterocyclic drugs for the treatment of infectious diseases has undergone a resurgence in recent years. Here we review the current status of monocyclic and bicyclic nitroheterocyclic compounds as existing or potential new treatments for visceral leishmaniasis, Chagas' disease and human African trypanosomiasis. Both monocyclic (nifurtimox, benznidazole and fexinidazole) and bicyclic (pretomanid (PA-824) and delamanid (OPC-67683)) nitro-compounds are prodrugs, requiring enzymatic activation to exert their parasite toxicity. Current understanding of the nitroreductases involved in activation and possible mechanisms by which parasites develop resistance is discussed along with a description of the pharmacokinetic / pharmacodynamic behaviour and chemical structure-activity relationships of drugs and experimental compounds.
| Original language | English |
|---|---|
| Pages (from-to) | 4454-4475 |
| Number of pages | 22 |
| Journal | Current Medicinal Chemistry |
| Volume | 26 |
| Issue number | 23 |
| Early online date | 26 Apr 2018 |
| DOIs | |
| Publication status | Published - 2019 |
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Keywords
- Chagas' disease
- Human African trypanosomiasis
- benznidazole
- delamanid
- fexinidazole
- nifurtimox
- nitro-drugs
- pretomanid
- visceral leishmaniasis.
Cite this
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Current and Future Prospects of Nitro-compounds as Drugs for Trypanosomiasis and Leishmaniasis. / Fairlamb, Alan H. (Lead / Corresponding author); Patterson, Stephen.
In: Current Medicinal Chemistry, Vol. 26, No. 23, 2019, p. 4454-4475.Research output: Contribution to journal › Review article
TY - JOUR
T1 - Current and Future Prospects of Nitro-compounds as Drugs for Trypanosomiasis and Leishmaniasis
AU - Fairlamb, Alan H.
AU - Patterson, Stephen
N1 - This work was funded by the Wellcome Trust (079838)
PY - 2019
Y1 - 2019
N2 - Interest in nitroheterocyclic drugs for the treatment of infectious diseases has undergone a resurgence in recent years. Here we review the current status of monocyclic and bicyclic nitroheterocyclic compounds as existing or potential new treatments for visceral leishmaniasis, Chagas' disease and human African trypanosomiasis. Both monocyclic (nifurtimox, benznidazole and fexinidazole) and bicyclic (pretomanid (PA-824) and delamanid (OPC-67683)) nitro-compounds are prodrugs, requiring enzymatic activation to exert their parasite toxicity. Current understanding of the nitroreductases involved in activation and possible mechanisms by which parasites develop resistance is discussed along with a description of the pharmacokinetic / pharmacodynamic behaviour and chemical structure-activity relationships of drugs and experimental compounds.
AB - Interest in nitroheterocyclic drugs for the treatment of infectious diseases has undergone a resurgence in recent years. Here we review the current status of monocyclic and bicyclic nitroheterocyclic compounds as existing or potential new treatments for visceral leishmaniasis, Chagas' disease and human African trypanosomiasis. Both monocyclic (nifurtimox, benznidazole and fexinidazole) and bicyclic (pretomanid (PA-824) and delamanid (OPC-67683)) nitro-compounds are prodrugs, requiring enzymatic activation to exert their parasite toxicity. Current understanding of the nitroreductases involved in activation and possible mechanisms by which parasites develop resistance is discussed along with a description of the pharmacokinetic / pharmacodynamic behaviour and chemical structure-activity relationships of drugs and experimental compounds.
KW - Chagas' disease
KW - Human African trypanosomiasis
KW - benznidazole
KW - delamanid
KW - fexinidazole
KW - nifurtimox
KW - nitro-drugs
KW - pretomanid
KW - visceral leishmaniasis.
UR - http://www.scopus.com/inward/record.url?scp=85073466165&partnerID=8YFLogxK
U2 - 10.2174/0929867325666180426164352
DO - 10.2174/0929867325666180426164352
M3 - Review article
C2 - 29701144
VL - 26
SP - 4454
EP - 4475
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
SN - 0929-8673
IS - 23
ER -