“…The three-dimensional image illustrating the molecular docking between the urea scaffin and the LmPTR1 is shown in Figure 3b. Studies of the biological potential of pentamidine antileishmania isethionate, through in vitro assays in promastigotes and amastigotes of L. donovani, show an action inhibition of 8.31μM for promastigote forms and 2.7 μM for amastigote forms 18. We can observe that the same drug being indicated for VL treatments has activity against L. major species, through these in silico studies by molecular docking, we obtainfavorable results showing the drug as a possible alternative against L. major species.…”
Avaliação por acoplamento molecular de inibidores da enzima pteridina redutase 1 de Leishmania Evaluación del acoplamiento molecular de los principales inhibidores de la pteridina reductasa 1
“…The three-dimensional image illustrating the molecular docking between the urea scaffin and the LmPTR1 is shown in Figure 3b. Studies of the biological potential of pentamidine antileishmania isethionate, through in vitro assays in promastigotes and amastigotes of L. donovani, show an action inhibition of 8.31μM for promastigote forms and 2.7 μM for amastigote forms 18. We can observe that the same drug being indicated for VL treatments has activity against L. major species, through these in silico studies by molecular docking, we obtainfavorable results showing the drug as a possible alternative against L. major species.…”
Avaliação por acoplamento molecular de inibidores da enzima pteridina redutase 1 de Leishmania Evaluación del acoplamiento molecular de los principales inhibidores de la pteridina reductasa 1
“… Within cyclic derivatives, it seemed that the replacement of 2-carbonyl with 2- thiocarbonyl moiety had a significant effect on antileishmanial inhibitory activity ( 24 ). Compound A10 (IC50: 52.67 μg/mL) and A11 (IC50: 182.55 μg/mL) were only structurally different concerning their C4 position in DHPM ring.…”
Section: Discussionmentioning
confidence: 99%
“…Within cyclic derivatives, it seemed that the replacement of 2-carbonyl with 2- thiocarbonyl moiety had a significant effect on antileishmanial inhibitory activity ( 24 ).…”
Background and purpose:
The prevalence of leishmaniasis is reported in more than 98 countries and Iran is one of the endemic areas. There is no vaccine for this disease and few effective drugs are available to treat it. Moreover, drug resistance to the disease is increasing. During the past decade, several
in vitro
and
in vivo
studies have been performed on dihydropyrimidine derivatives as antileishmanial agents.
Experimental approach:
In the present project, a few 6-methyl-4-aryl-
N
-aryl dihydropyrimidinone/thiones (
A7-A11
) and
N
-heteroaryl-3-(
para
-methoxy benzyl) amino but-enamides (A1-A6) were synthesized, structurally characterized, and finally subjected to
in vitro
anti-leishmanial effect against
Leishmania major
promastigotes.
Findings / Results:
Results of the study showed that compound
A10
, 4-(3-chlorophenyl)-6-methyl-
N
-phenyl- 2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide, exhibited superior anti-leishmanial effect with IC50 value of 52.67 µg/mL (more active than standard drug Glucantim® with IC50 71000 ± 390 µg/mL).
Conclusion and implications:
It was demonstrated that some dihydropyrimidine thiones were able to inhibit Leishmania major promastigotes. Structure-activity relationship evaluations indicated that more electron-poor rings such as isoxazole afforded higher activity within
A1-A6
series and in these derivatives,
N
-benzothiazole rings reinforced anti-leishmanial activity concerning thiazole. It was also observed that higher anti-parasite activities of
A10
and
A11
concerning
A7-A9
might be related to the incorporation of the sulfur atom into C2 position, replacement of N-thiazole carboxamide by N-phenyl carboxamide on C5 position of dihydropyrimidine ring, and also replacement of
para
with
meta
-substituted phenyls within C4 of dihydropyrimidine ring. The results may help unveil new 4-aryl-5-carboxamide dihydropyrimidines as potential anti-leishmanial agents and their further structural modification toward more potent derivatives.
“…HCl and HOBt with various substituted phenyl piperazines lead to the synthesis of various 3- substituted β-carboline phenyl piperazines ( Ashok et al., 2017 ), ( Ashok et al., 2018 ) ( Scheme 10 ). In the subsequent year, the same research group was also explored the successful methylation at the NH in the 9th position by using methyl iodide ( Ashok et al., 2019 ) ( Scheme 11 ). 1-phenyl 1,2,3,4-tetrahydro-β-carboline derivatives also reported by the same research group by taking tryptamine as a starting material.…”
Section: Synthetic Strategiesmentioning
confidence: 99%
“…reported the synthesis of piperazinyl-β-carboline-3-carboxamide derivatives and evaluated their anti-leishmanial activity against Leishmania infantum and Leishmania donovani . Among the reported derivatives, compounds 124, 125, and 126 exhibited potent inhibition of promastigotes (EC 50 1.59, 1.47, and 3.73 μM, respectively) and amastigotes (EC 50 1.4, 1.9 and 2.6 μM respectively) of L. infantum ( Ashok et al., 2019 ) (see Figure 4 ). Figure 4 Structure of compounds 124, 125 and 126 .…”
Leishmaniasis is the most widespread pathogenic disease in several countries. Currently, no effective vaccines are available, and the control of Leishmaniasis primarily relies on decade-old chemotherapy. The treatment for the Leishmaniasis is not up to the mark. Current therapy for Leishmaniasis is ancient and requires hospitalization for the administration. These medications are also highly toxic and resistant. β-carboline, a natural indole containing alkaloid, holds a vital position in the field of medicinal chemistry with a diversified pharmacological action. The current review focuses mainly on the anti-leishmanial effects of β-carboline analogs and their synthetic strategies, structural activity relationship studies (SAR). The past ten years alterations unveiled by β-carboline analogs present in phytoconstituents and various derivatives of synthesized analogs with the mechanism of action were briefly shortlisted and illustrated.
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