Synthesis of structural analogues of hexadecylphosphocholine and their antineoplastic, antimicrobial and amoebicidal activity

Timko, Lukáš; Fischer‐Fodor, Eva; Garajová, Mária; Mrva, Martin; Cherecheș, Gabriela; Ondriska, František; Bukovský, Marián; Lukáč, Miloš; Karlovská, Janka; Kubincová, Janka; Devı́nsky, Ferdinand

doi:10.1016/j.ejmech.2015.02.014

Cited by 9 publications

(9 citation statements)

References 49 publications

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“…APCs and QACs are effective antimicrobials against fungi, bacteria, some protists and also have anti-tumour properties. In this study, we have confirmed their toxicity against Acanthamoeba trophozoites 34,35 , and showed that QACs were more effective than their APCs counterpart, perhaps due to the formation of larger micelles (QACs, 8.8 ± 0.8 nm; APCs, 5.8 ± 1.0 nm) 36 . Interestingly, the activities from both compound-types were strongly correlated with their alkyl-carbon chain lengths against trophozoites, a key indicator for micellar size and hydrophobicity.…”

Section: Discussionsupporting

confidence: 65%

Alkyl-carbon chain length of two distinct compounds and derivatives are key determinants of their anti-Acanthamoeba activities

Mooney

Masala

Martial

et al. 2020

Sci Rep

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the opportunistic pathogen, Acanthamoeba castellanii is the causative agent for the sight threatening infection Acanthamoeba keratitis (AK). it is commonly associated with contact lens wearers, and prevalence is increasing at an alarming rate due to an inadequate preventive strategy to protect the lens from this protist. This problem is compounded by the lack of an effective acanthamoebocide, particularly with cysticidal activity in the contact lens solutions. We have used cytotoxicity assays and a variety of biophysical approaches to show that two molecules with tails made of alkyl carbon, alkylphosphocholines (APCs) and quaternary ammonium compounds (QACs) had significant chain-length dependent efficacy against A. castellanii trophozoites, the latter producing death via permeabilization, and DNA complexing. QACs were more effective than APCs and had activity against cysts. Conversely, the QAC with 12 alkyl carbon chain, was non toxic, its presence increased A. castellanii trophozoites biomass and delayed encystation by 96 h. Interestingly, it was unable to induce excystation and increased trophozoite sensitivity to APC16. These results present a mono-and multi-inhibitor management strategy effective against trophozoites and cysts that may be useful for formulating into contact lense cleaning solutions and reducing AK incidence. Acanthamoeba are free-living protists, existing as active trophozoites and non-replicative cysts characterised by double cellulose cell walls 1. They have opportunistic tendencies and can cause the diseases, Acanthamoeba keratitis (AK), cutaneous acanthamoebiasis (CA) and granulomatous amoebic encephalitis (GAE) 2,3. Whilst CA and GAE are lethal but rare and affect the skin and CNS, respectively, the non-lethal AK causes severe infection in the cornea, threatening sight loss and causing emotional and psychological trauma, described as life-changing in patients 4. Trophozoites to cysts interconversion and vice versa (encystation and excystation) is induced by external environmental cues 5,6 and poses significant challenges for curative treatment particularly causing AK resurgences and relapses 7. AK cases are increasing and prevalence is high amongst contact lens users 8,9. Cases of AK within the UK have risen drastically within the last 20 years and continue to do so 10. The reason for this upsurge in incidence rates does not appear to be as a result of increased lens wearers but is as of yet unknown, likely the result of multiple factors 10. Spatial geographic differences are common with 15 times more cases reported in the UK than the USA 11,12 , and 8 times more in Scotland than England 13. These differences are strongly linked with water supply, quality and usage 12. Indeed, the incidence of AK in contact lens users is believed to be due to rinsing of contact lenses with domestic tap water 14. Further, the lack of anti-acanthamoebocides in cleaning solutions is another issue. Despite the presence of preservative compounds such as polyhexamethylene biguanide used in existing solutions,...

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Section: Discussionsupporting

confidence: 65%

Alkyl-carbon chain length of two distinct compounds and derivatives are key determinants of their anti-Acanthamoeba activities

Mooney

Masala

Martial

et al. 2020

Sci Rep

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“…The yields of this reaction were comparable to those reported in the literature. [33] The 18-and 20-carbon alkyl tosylates were prepared by following the standard procedure [34] using octadecyl and eicosoyl alcohol, respectively.…”

Section: General Procedures For the Preparation Of 4-toluenesulphonatementioning

confidence: 99%

Thermotropic liquid-crystalline properties of extended viologen bis(triflimide) salts

Bhowmik

Killarney

et al. 2017

Liquid Crystals

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A series of extended, symmetric viologen triflimides were synthesized by the metathesis reaction of lithium triflimide with the respective viologen tosyalates in methanol. Their chemical structures were characterized by Fourier Transform Infrared, 1 H and 13 C Nuclear Magnetic Resonance spectroscopy and elemental analysis. Their thermotropic liquid-crystalline (LC) properties were examined by a number of experimental techniques including differential scanning calorimetry, thermogravimetric analysis, polarizing optical microscopy and variable temperature X-ray diffraction. The viologen salts containing alkyl chain of two carbon and three carbon atoms were relatively low melting salts. Those of alkyl chains of four carbon and five carbon atoms formed ionic liquids at 88 and 42 °C, respectively. Those of alkyl chain of nine, ten and eleven carbon atoms were high melting salts as high as 166 °C. Those of higher alkyl chains of sixteen, eighteen and twenty carbon atoms showed thermotropic LC phases forming SmC, SmA and an unidentified smectic (Sm) phases, and showed SmA to isotropic transitions at high temperatures. As expected, all the viologen triflimides had excellent stabilities in the temperature range of 338-365 °C.

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“…Timko et al, 86 synthesised a series of 12 analogues of hexadecylphosphocholine. The study was designed to examine the effect of length and position of alkyl chain in these compounds on the biological activities.…”

Section: Medicinal Chemistry Approach For Drug Discovery Against Acan...mentioning

confidence: 99%

“…The compounds did not show any antibacterial activity against any of the bacterium used in the experiment. The change in position of a long hydrocarbon chain within the structure with maximum efficacy was observed for antitumour, antiprotozoal and antifungal activity 86 …”

Section: Medicinal Chemistry Approach For Drug Discovery Against Acan...mentioning

confidence: 99%

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Applications of medicinal chemistry for drug discovery against Acanthamoeba infections

Ahmed

Anwar

Ong

et al. 2021

Medicinal Research Reviews

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Acanthamoeba is a genus of free‐living amoebae, pervasively found in the environment. Most of its pathogenic species are the causative agent of sight‐threatening Acanthamoeba keratitis and fatal granulomatous amoebic encephalitis. Despite the advancements in the field of chemotherapy, treating Acanthamoeba infections is still challenging due to incomplete knowledge of the complicated pathophysiology. In case of infection, the treatment regimen for the patients is often ineffective due to delayed diagnosis, poor specificity, and side‐effects. Besides the resistance of Acanthamoeba cysts to most of the drugs, the recurrence of infection further complicates the recovery. Thus, it is necessary to develop an effective treatment which can eradicate these rare, but serious infections. Based on various computational and in vitro studies, it has been established that the synthetic scaffolds such as heterocyclic compounds may act as potential drug leads for the development of antiamoebic drugs. In this review, we report different classes of synthetic compounds especially heterocyclic compounds which have shown promising results against Acanthamoeba. Moreover, the antiamoebic activities of synthetic compounds with their possible mode of actions against Acanthamoeba, have been summarized and discussed in this review.

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Synthesis of structural analogues of hexadecylphosphocholine and their antineoplastic, antimicrobial and amoebicidal activity

Cited by 9 publications

References 49 publications

Alkyl-carbon chain length of two distinct compounds and derivatives are key determinants of their anti-Acanthamoeba activities

Alkyl-carbon chain length of two distinct compounds and derivatives are key determinants of their anti-Acanthamoeba activities

Thermotropic liquid-crystalline properties of extended viologen bis(triflimide) salts

Applications of medicinal chemistry for drug discovery against Acanthamoeba infections

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