Derivatives of pentamidine designed to target the Leishmania lipophosphoglycan

Kramp, Kari; DeWitt, Kristin; Flora, Jason W.; Muddiman, David C.; Slunt, K M; Houston, Todd Ashley

doi:10.1016/j.tetlet.2004.11.112

Cited by 13 publications

(5 citation statements)

References 30 publications

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“…We have found that use of a glycerol matrix for fast atom bombardment (FAB) ionization is particularly useful for mass spectrometric characterization of diboronate species. [31] While other techniques are used in the study of boron-polyol complexes, those mentioned here are among the most common routinely used in the field today.…”

Section: Fundamentals Of Boron-diol Exchangementioning

confidence: 99%

Boron-Carbohydrate Interactions

Pappin¹,

Kiefel²,

Houston³

2012

Carbohydrates - Comprehensive Studies on Glycobiology and Glycotechnology

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Section: Fundamentals Of Boron-diol Exchangementioning

confidence: 99%

Boron-Carbohydrate Interactions

Pappin¹,

Kiefel²,

Houston³

2012

Carbohydrates - Comprehensive Studies on Glycobiology and Glycotechnology

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“…One such attempt was made, to modify the PTM using boronic acid to target the leishmanial membrane lipophosphoglycan. But the results of the study were not satisfactory [ 65 ]. In another meaningful attempt, MA with a low polymerized state has been developed which exhibited considerable oral absorption [ 66 ].…”

Section: Strategies To Overcome Anti-leishmanials Associated Limitationsmentioning

confidence: 99%

Nanotechnology based solutions for anti-leishmanial impediments: a detailed insight

2021

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As a neglected tropical disease, Leishmaniasis is significantly instigating morbidity and mortality across the globe. Its clinical spectrum varies from ulcerative cutaneous lesions to systemic immersion causing hyperthermic hepato-splenomegaly. Curbing leishmanial parasite is toughly attributable to the myriad obstacles in existing chemotherapy and immunization. Since the 1990s, extensive research has been conducted for ameliorating disease prognosis, by resolving certain obstacles of conventional therapeutics viz. poor efficacy, systemic toxicity, inadequate drug accumulation inside the macrophage, scarce antigenic presentation to body’s immune cells, protracted length and cost of the treatment. Mentioned hurdles can be restricted by designing nano-drug delivery system (nano-DDS) of extant anti-leishmanials, phyto-nano-DDS, surface modified—mannosylated and thiolated nano-DDS. Likewise, antigen delivery with co-transportation of suitable adjuvants would be achievable through nano-vaccines. In the past decade, researchers have engineered nano-DDS to improve the safety profile of existing drugs by restricting their release parameters. Polymerically-derived nano-DDS were found as a suitable option for oral delivery as well as SLNs due to pharmacokinetic re-modeling of drugs. Mannosylated nano-DDS have upgraded macrophage internalizing of nanosystem and the entrapped drug, provided with minimal toxicity. Cutaneous Leishmaniasis (CL) was tackling by the utilization of nano-DDS designed for topical delivery including niosomes, liposomes, and transfersomes. Transfersomes, however, appears to be superior for this purpose. The nanotechnology-based solution to prevent parasitic resistance is the use of Thiolated drug-loaded and multiple drugs loaded nano-DDS. These surfaces amended nano-DDS possess augmented IC50 values in comparison to conventional drugs and un-modified nano-DDS. Phyto-nano-DDS, another obscure horizon, have also been evaluated for their anti-leishmanial response, however, more intense assessment is a prerequisite. Impoverished Cytotoxic T-cells response followed by Leishmanial antigen proteins delivery have also been vanquished using nano-adjuvants. The eminence of nano-DDS for curtailment of anti-leishmanial chemotherapy and immunization associated challenges are extensively summed up in this review. This expedited approach is ameliorating the Leishmaniasis management successfully. Alongside, total to partial eradication of this disease can be sought along with associated co-morbidities.

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“…The authors [29] showed that the pentamidine derivatives (1) and its diboronate analogues (2) Dorota Maciejewska et al described the synthesis of four new 1,5-bis(4-amidinophenoxy)-3-oxapentane analogs (5) [30]. The synthesis was performed via condensation of 4-hydroxy-benzonitrile with 1-chloro-2-(2-chloroethoxy)ethane to give compound 3, that was subsequently converted into 4, via a Pinner reaction [8] and then into compounds 5 (Scheme 1).…”

Section: Synthesis Of Pentamidine Analoguesmentioning

confidence: 99%

“…A small library of 2,2'-[( , -alkanediylbis(oxyphenylene)]bis-1H-benzimidazoles (29) has been prepared by Vanden Eynde et al and screened in vitro against Pneumocystis carinii, Trypanosoma brucei rhodesiense, and Leishmania donovani. Among the six tested compounds two derivatives emerged as promising hits characterized by IC50 values lower than that determined for pentamidine against L. donovani [43].…”

Section: Cnmentioning

confidence: 99%

New Pentamidine Analogues in Medicinal Chemistry

Porcheddu¹,

Giacomelli²,

Luca³

2012

CMC

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Sixty years after its introduction, 1,5-bis(4-amidinophenoxy)pentane (Pentamidine) is still one of the most used drugs for the treatment of the first stage of Human African trypanosomiasis and other neglected diseases such as malaria and leishmaniasis. These protozoan infections are prevalent in the poorest world areas such as sub-saharian and developing countries, however the increasing immigration from these countries to the richest part of the world and the overlap of HIV with parasitic infections result in a growing number of cases in developed nations. A great effort has been made to develop new generations of diamidines for the treatment of these infections transmitted by insects. This review summarises the synthesis and evaluation of pentamidine analogues reported in the last years in the effort to find new drugs with better pharmaceutical activity, higher lipophilicity and lower citotoxycicty.

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Derivatives of pentamidine designed to target the Leishmania lipophosphoglycan

Cited by 13 publications

References 30 publications

Boron-Carbohydrate Interactions

Boron-Carbohydrate Interactions

Nanotechnology based solutions for anti-leishmanial impediments: a detailed insight

New Pentamidine Analogues in Medicinal Chemistry

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