Delving into the Latest Updates on Meglumine Antimoniate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Glucantim, Meglumine antimonate

+ [1]

Target-

Action-

Mechanism-

Therapeutic Areas

Infectious DiseasesSkin and Musculoskeletal DiseasesOther Diseases

Active Indication

Leishmaniasis

Inactive Indication-

Originator Organization

Sanofi

Active Organization

Sanofi

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC7H18NO8Sb

InChIKeyJLGCKKAHTCRITP-SESJOKTNSA-O

CAS Registry133-51-7

View All Structures (2)

BACKGROUNDIncreasing resistance to antimonial drugs has become a significant challenge in effective treatment in endemic regions of leishmaniasis. Antioxidant defense plays a crucial role in antimony resistance by combating antimonial-induced oxidative stress. Accordingly, we investigated the transcript levels of some antioxidant genes in antimony-sensitive and resistant clinical Leishmania tropica isolates.METHODSIn the current study, 22 Leishmania tropica isolates from ACL patients who presented responsive or unresponsive to antimony were examined. The susceptibility of parasites against SbV and hydrogen peroxide (H₂O₂) was analyzed. We evaluated the transcript levels of five genes, including cytosolic and mitochondrial tryparedoxin (cTXN, mTXN), cytosolic and mitochondrial tryparedoxin peroxidase (cTXNPx, mTXNPx), and ascorbate peroxidase (APX) in antimony-sensitive and resistant L. tropica clinical isolates.RESULTSThe in-vitro susceptibility to SbV in intracellular amastigotes revealed 3.82 times higher IC₅₀ in resistant isolates compared to sensitive ones. The IC₅₀ toward H₂O₂ in resistant isolates was 1.6 times higher than in sensitive ones, positively correlated with SbV IC₅₀ values. The average transcript expression level of cTXNPx, mTXNPx, cTXN, and APX genes significantly increased in resistant isolates by 2.51, 1.69, 2.41, and 2.12-fold compared to sensitive ones. The highest correlation coefficient between the gene expression and SbV IC₅₀ values belonged to the cTXNPx, cTXN, APX, mTXN, and mTXNPx genes, respectively. The average transcript expression level of cytosolic TXN and TXNPx in resistant L. tropica isolates was higher than its mitochondrial counterpart.CONCLUSIONSThe data presented here revealed a phenotypic heterogeneity in antioxidant gene expression among L. tropica clinical isolates. Overall, the upregulation of genes involved in antioxidant defense could probably contribute to natural antimony resistance in L. tropica clinical isolates.

01 Jun 2025·European Journal of Medicinal Chemistry

Exploring chloro-isoxazole compounds inspired on tetrahydrofuran neolignans as promising antileishmanial agents

Article

Author: Oliveira, Kelly M P ; Piranda, Eliane M ; Baroni, Adriano C M ; das Neves, Amarith R ; Arruda, Carla C P ; Machado, Erika P ; Hurtado, Gabriela R ; Pereira, Luiz F P ; Rosalem, Rafael F ; Kassab, Najla M ; Shiguemoto, Cristiane Y K ; Castilho, Pamella F ; Ferreira, Alda M T ; Orofino, Rafael S ; Carvalho, Diego B ; Riul, Thalita B ; Silva, Gleice K G ; Silva, Fernanda

The present work aims to synthesize and to identify a potential antileishmanial agent from chloro-diphenyl isoxazole methoxylated compounds. We have synthesized ten new chloro-isoxazole analogs inspired by the scaffold of tetrahydrofuran neolignans veraguensin 1a, grandisin 1b, and machilin G 1c. To obtain analogs 4a-4j, we used a cycloaddition reaction with yields ranging from 45 % to 89 %. All compounds were characterized using Nuclear Magnetic Resonance of ¹H and ¹³C and analyzed by using High-Resolution Mass Spectrometry. The HPLC analysis confirmed that all compounds were more than 95 % pure. Finally, we tested the antileishmanial activity of these analogs against promastigote and intracellular amastigote forms of L. amazonensis in vitro. We conducted tests on murine peritoneal macrophages to determine the cytotoxicity of the analogs. Our findings revealed that 4e (R₁-R₃ = -OCH₃, X₁ = -Cl, R₄ and R₅ = -OCH₂O-), a hybrid compound of grandisin and machilin G, showed moderate activity on promastigotes (IC₅₀ = 38.1 ± 1.5 μM). 4e was also effective against intracellular amastigotes with similar IC₅₀ values to AmB-treated control (IC₅₀ = 2.2 ± 0.4 μM and IC₅₀ = 2.0 ± 0.1, respectively). Moreover, it exhibited a selectivity index (SI) for amastigote forms equal to 22.7, higher than the reference drugs we tested. Analog 4e displayed non-mutagenic potential at all tested concentrations in the Ames test. We also evaluated the therapeutic effect of 4e on the experimental cutaneous leishmaniasis model with BALB/c mice infected with promastigote forms of L. amazonensis and treated with intralesional (IL) injections. Our study found that mice treated with 4e had a significant reduction (99.5 % drop) in the footpad tissue parasite load compared to the control group treated with the vehicle. The effect of 4e was similar, controlling the infection, to that of N-methylglucamine antimonate (Sb, Glucantime, 99.8 % drop), which is a reference treatment. Based on our results, we suggest that chloro-isoxazole analog 4e shows potential as an antileishmanial agent for treating cutaneous leishmaniasis (CL).

01 Jun 2025·Fluid Phase Equilibria

Hydrophobic interactions described using hetero-segmented PC-SAFT: 2. Surfactants and their aqueous solutions

Author: Sadowski, Gabriele ; Rother, Marius

Despite their importance for industry and pharmaceuticals applications, description of aqueous solutions that contain surfactants is still a challenging task in thermodn. modeling.As a first step towards a holistic modeling approach, which is also applicable for concentrated surfactant solutions, this work aimed to model the intrinsic behavior of surfactant mols.For this purpose, we applied hetero-segmented PC-SAFT as a group contribution method to build surfactant mols. from different groups, which sep. characterize the hydrophobic tail and the hydrophilic head of the surfactant.While the hydrophobic tail is modeled by the parameterization developed in the first part of this paper series (M. Rother, G. Sadowski, Fluid Phase Equilibrium 582 (2024)), this work focuses on extending the parameter matrix to model the hydrophilic head.We considered the surfactant classes C_iG₁, C_iE_j and MEGA-i.The parameters for the surfactant head groups were adjusted to sorption data of surfactant/alc. systems and to partition coefficients of the surfactants in n-alkane/water systems and n-alc./water systems.As a benchmark of the new parameterization, we modeled the critical micelle concentration as a function of temperature for these three surfactant classes using a newly developed, explicit equation for calculating this quantity.The results are in even quant. agreement with the exptl. data.

100 Deals associated with Meglumine Antimoniate

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Meglumine Antimoniate	P01CB01	DB13732

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Leishmaniasis	-	Sanofi	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


WCD2023	Not Applicable	Leishmaniasis, Cutaneous	32	Sbv + G-CSF	sowpplxnpi(cmwcagsjvn) = qtqhknpmeh rvpmcsgwgb (oysoviswnm )	Positive	03 Jul 2023
				Sbv + Placebo	sowpplxnpi(cmwcagsjvn) = pryopdwbhg rvpmcsgwgb (oysoviswnm )
NCT03023111 (Pubmed \| Int J Infect Dis)	Phase 3	Leishmaniasis, Cutaneous	150	Topical GM-CSF + Miltefosine	pubfepejxm(lieinjgztu) = One patient (group MA) stopped treatment after presenting with fever, exanthema, and severe arthralgia rorovwvolo (avrgqdofwz ) View more	-	01 Feb 2021
				Placebo + Miltefosine
NCT01462500 \| NCT00487253 \| NCT01464242 (Pubmed \| PLoS Negl Trop Dis)	Not Applicable	Leishmaniasis, Cutaneous	-	miltefosine	ijdmwxazmh(drkrpxbeex) = umuxpunoiv vtdeerrecn (vyplcttdhq, 3.59 - 14.26)	-	01 Apr 2017
				meglumine antimoniate	ijdmwxazmh(drkrpxbeex) = ulleevyndk vtdeerrecn (vyplcttdhq, 14.48 - 29.58)
NCT00487253 (Pubmed \| J Infect Dis)	Phase 3	Leishmaniasis, Cutaneous	116	Miltefosine	(qpnmzvwxeq) = nicsqgdkeg faeyegufgf (eonxbcpgun, 5.7% - 28.7%)	Positive	15 Feb 2012
				Meglumine antimoniate	(qpnmzvwxeq) = lwumutcydb faeyegufgf (eonxbcpgun, 16.9% - 45.2%)