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Mini review on tricyclic compounds as an inhibitor of trypanothione reductase.

Kumar S, Ali MR, Bawa S - J Pharm Bioallied Sci (2014)

Bottom Line: Trypanosomiasis and leishmaniasis are two most ruinous parasitic infectious diseases caused by Trypanosoma and Leishmania species.The disease affects millions of people all over the world and associated with high morbidity and mortality rates.In this review we have tried to present an overview of the different tricyclic compounds which are potent inhibitors of TryR with their inhibitory activities against the parasites are briefly discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.

ABSTRACT
Trypanosomiasis and leishmaniasis are two most ruinous parasitic infectious diseases caused by Trypanosoma and Leishmania species. The disease affects millions of people all over the world and associated with high morbidity and mortality rates. The review discuss briefly on current treatment of these parasitic diseases and trypanothione reductase (TryR) as potential targets for rational drug design. The enzyme trypanothione reductase (TryR) has been identified as unique among these parasites and has been proposed to be an effective target against for developing new drugs. The researchers have selected this enzyme as target is due to its substrate specificity in contrast to human analogous glutathione reductase and its absence from the host cell which makes this enzyme an ideal target for drug discovery. In this review we have tried to present an overview of the different tricyclic compounds which are potent inhibitors of TryR with their inhibitory activities against the parasites are briefly discussed.

No MeSH data available.


Related in: MedlinePlus

Potential compounds from different literature
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Figure 6: Potential compounds from different literature

Mentions: A study done by Chibale et al.[15] reported design and synthesis of 9, 9-dimethylxanthene derivatives (9-14) as potential inhibitor of TR. They designed target compounds in which 9, 9-dimethylxanthene ring was exploited as an aromatic hydrophobic tricyclic moiety that bears resemblance to the aromatic hydrophobic tricyclic moieties found in other tricyclic compounds already reported as competitive inhibitors of TR, where the tricyclic moiety binds in the hydrophobic pocket involved in recognition of the spermidine moiety of trypanothione disulfide, the substrate for TR. Moreover, in 9, 9-dimethylxanthene system potential multiple sites are provided by chemically reactive 2, 7 and 4, 5 positions for introducing chemical diversity. Apart from these functions, they also introduced terminal tertiary amino group (exemplified by the dimethylamino group) into compounds (9-14) to provide a positive charge which has been shown to favor TryR over GR, the closest related host enzyme. Thorough analysis of results of TryR inhibitions study [Table 2], it was found that compounds (9-11) bearing either one (10) or no methylene spacer (9 and 11) between the tricyclic moiety and the secondary nitrogen atom generally show weaker inhibition of TR compared to derivatives with two or three carbon methylene spacer (12, 13 and 14) [Figure 6].


Mini review on tricyclic compounds as an inhibitor of trypanothione reductase.

Kumar S, Ali MR, Bawa S - J Pharm Bioallied Sci (2014)

Potential compounds from different literature
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231380&req=5

Figure 6: Potential compounds from different literature
Mentions: A study done by Chibale et al.[15] reported design and synthesis of 9, 9-dimethylxanthene derivatives (9-14) as potential inhibitor of TR. They designed target compounds in which 9, 9-dimethylxanthene ring was exploited as an aromatic hydrophobic tricyclic moiety that bears resemblance to the aromatic hydrophobic tricyclic moieties found in other tricyclic compounds already reported as competitive inhibitors of TR, where the tricyclic moiety binds in the hydrophobic pocket involved in recognition of the spermidine moiety of trypanothione disulfide, the substrate for TR. Moreover, in 9, 9-dimethylxanthene system potential multiple sites are provided by chemically reactive 2, 7 and 4, 5 positions for introducing chemical diversity. Apart from these functions, they also introduced terminal tertiary amino group (exemplified by the dimethylamino group) into compounds (9-14) to provide a positive charge which has been shown to favor TryR over GR, the closest related host enzyme. Thorough analysis of results of TryR inhibitions study [Table 2], it was found that compounds (9-11) bearing either one (10) or no methylene spacer (9 and 11) between the tricyclic moiety and the secondary nitrogen atom generally show weaker inhibition of TR compared to derivatives with two or three carbon methylene spacer (12, 13 and 14) [Figure 6].

Bottom Line: Trypanosomiasis and leishmaniasis are two most ruinous parasitic infectious diseases caused by Trypanosoma and Leishmania species.The disease affects millions of people all over the world and associated with high morbidity and mortality rates.In this review we have tried to present an overview of the different tricyclic compounds which are potent inhibitors of TryR with their inhibitory activities against the parasites are briefly discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.

ABSTRACT
Trypanosomiasis and leishmaniasis are two most ruinous parasitic infectious diseases caused by Trypanosoma and Leishmania species. The disease affects millions of people all over the world and associated with high morbidity and mortality rates. The review discuss briefly on current treatment of these parasitic diseases and trypanothione reductase (TryR) as potential targets for rational drug design. The enzyme trypanothione reductase (TryR) has been identified as unique among these parasites and has been proposed to be an effective target against for developing new drugs. The researchers have selected this enzyme as target is due to its substrate specificity in contrast to human analogous glutathione reductase and its absence from the host cell which makes this enzyme an ideal target for drug discovery. In this review we have tried to present an overview of the different tricyclic compounds which are potent inhibitors of TryR with their inhibitory activities against the parasites are briefly discussed.

No MeSH data available.


Related in: MedlinePlus