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BACKGROUND: Botrytis cinerea, the causal agent of gray mold, is one of the top 10 fungal pathogens in the world. Propamidine, an aromatic diamidine compound, exhibited both protective and therapeutic effects against B. cinerea. However, the resistance risk and mechanism of B. cinerea to propamidine are unclear. RESULTS: Twelve high and stable resistant mutants were obtained from B. cinereaB05.10 by fungicide induction. Compared with the parental strain, the biological fitness of the mutants, including growth rate, spore germination, pathogenicity, and oxalic acid decreased significantly. There was no cross‐resistance among propamidine and other commonly used fungicides, while the efficacy of propamidine against the resistance mutants declined. In addition, the cell membrane permeability, substance metabolism, and defense enzyme activities of the resistant mutants were significantly increased compared with the wild strain. Whole‐genome sequencing of all resistant mutants found that there were 32 SNPs and nine InDels. Importantly, nine common single‐point mutant genes in the exon region were found in all 12 resistant mutants, and these genes were related to multiple pathways in vivo, indicating that many factors contributed to the formation of propamidine resistance. CONCLUSION: These data suggested the resistance risk of B. cinerea to propamidine was low to moderate and the mechanism of propamidine was different from that of the existing fungicides. These results will increase understanding of the resistance mechanism of propamidine and provide a critical basis for the rational design of pesticide molecules based on targets. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objective: Review the clinical characteristics, diagnosis, treatment and visual results in patients diagnosed with Acanthamoeba keratitis (AK). Demonstrate the importance of early diagnosis and of prompt and effective treatment. Material and methods: Retrospective study of 14 eyes in the same number of patients diagnosed with AK, treated at Centro Visi?n between July 2008 and June 2012. All the cases were confirmed by smear and/or culture. Two groups were established: early and late diagnosis. Treatment was carried out with propamidine and polyhexamethylene biguanide. After the infection had been eliminated, final visual acuity and duration of treatment were recorded. Results: The most frequently affected group was aged between 21 and 40 years (9 cases). Only two eyes (14.3%) were correctly diagnosed initially as AK. Eleven patients (78.6%) were contact lens wearers. The most common sign was diffuse infiltrate (62.3%); perineural infiltrate was only seen in one case. Five patients were diagnosed within the first thirty days (early diagnosis group) and nine cases were diagnosed later (late diagnosis group). Median visual acuity in the early diagnosis group was 20/40, and in the late diagnosis group it was 20/400. The median duration of treatment in the early diagnosis group was six months, and in the late diagnosis group it was ten months. Conclusions: The majority of the eyes (85.7%) were initially erroneously classified as keratitis resulting from other causes. When AK is diagnosed early there is a better visual prognosis, and also prolonged treatment will not be necessary.

In the current study, baseline sensitivity of Valsa mali to propamidine was determined using 80 strains collected from apple orchards in Shaanxi Province, China. The median effective concentration (EC 50 ) values for propamidine inhibiting mycelial growth ranged from 0.086 to 0.852 μg/mL, with a mean of 0.405 ± 0.137 μg/mL. After treated with propamidine, mycelia were contorted with an increased number of branches, loss of fruiting body production, and decreased cell membrane permeability. Moreover, the enzyme activities of the complexes I, II, IV and ATPase in the mitochondrial respiratory chain were increased significantly, while the enzyme activities of complexes III decreased. Importantly, both on detached leaves and branches of apple trees, propamidine applied at 100 μg/mL exhibited over 75% protective and curative efficacies, which were even better than the efficacies obtained by carbendazim at the same concentration. These results indicated that propamidine could be used as an alternative compound in controlling Valsa canker and mitochondrial respiratory chains might be correlated with the action mode of propamidine. This study encourages further investigation for the action mechanism of propamidine against plant pathogens and the information could be valuable for synthesis of new antifungal drugs with novel modes of action. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcer (DFU) is becoming more serious concern as it affects 95% of diabetic patients worldwide. It has been shown that the Staphylococcus aureus and other Gram-negative microorganisms are the main reasons behind this disease. Though many antibiotics are presently used to treat the DFU, due to increased bacterial resistance, new alternative therapies are always welcome. To address this alarming issue, we have designed and synthesized the high-valence silver propamidine (Ag(II)PRO) complex as well as nanoparticles and characterized both by usual spectroscopic methods. The reverse microemulsion technique has been applied to synthesize Ag(II)PRO nanoparticles and its antibacterial activity has been compared with zero-valence silver nanoparticles (AgNPs) with similar size. The antibacterial efficacies of Ag(II)PRO nanoparticles and AgNPs were tested against Gram-negative and Gram -positive organisms responsible for DFU. The newly synthesized high-valence Ag(II)PRO nanoparticles showed higher antibacterial activity compared to silver-only nanoparticles (AgNPs). This study concludes that the high-valence Ag(II)PRO nanoparticles show better antibacterial activity than AgNPs and they may serve as the next generation therapeutic agent for the diabetic wound care. [ABSTRACT FROM AUTHOR]

Purpose: Acanthamoeba keratitis causes frequent epithelial lesions that fully expose the corneal stroma. The aim of this study was to determine the toxic profile of chlorhexidine and propamidine eye drops.Methods: We used primary human keratocytes in cell culture in combination with a novel technology that evaluates dynamic real-time cytotoxicity through impedance analysis. Additional studies such as a classic cell viability test (WST-1®), a bovine corneal opacity and permeability assay, and an irritation eye study (Hen's Egg Test [HET]) have been made.Results: Both eye drop formulations showed a time- and concentration-dependent toxicity profile, in which long periods and high concentrations were more detrimental to cells. In prolonged times of exposure, propamidine is more harmful to cells than chlorhexidine. On the contrary, no irritation has been detected in using the HET-chorioallantoic membrane test and no alterations in the corneal transparency nor permeability was produced by the treatment with both eye drops.Conclusions: In culture assay, chlorhexidine eye drops have proven to be less cytotoxic than Brolene® for a long contact period of time, but no signs of irritation or alterations in transparency or permeability have been observed in the cornea after both treatments. [ABSTRACT FROM AUTHOR]

Acanthamoeba keratitis is a sight-threatening infectious disease. Resistance of the cystic form of the protozoan to biocides and the potential toxicity of chemical compounds to corneal cells are the main concerns related to long-term treatment with the clinically available ophthalmic drugs. Currently, a limited number of recognized antimicrobial agents are available to treat ocular amoebic infections. Topical application of biguanide and diamidine antiseptic solutions is the first-line therapy. We consider the current challenges when treating Acanthamoeba keratitis and review the chemical properties, toxicities, and mechanisms of action of the available biocides. Antimicrobial therapy using anti-inflammatory drugs is controversial, and aspects related to this topic are discussed. Finally, we offer our perspective on potential improvement of the effectiveness and safety of therapeutic profiles, with the focus on the quality of life and the advancement of individualized medicine. [ABSTRACT FROM AUTHOR]

Propamidine is an aromatic diamidine compound. In the current study, baseline sensitivity of Sclerotinia sclerotiorum to propamidine was determined using 78 strains collected from the oilseed rape fields without a previous history of propamidine usage. The median effective concentration (EC 50 ) values for propamidine inhibiting mycelial growth ranged from 0.406 to 3.647 μg/mL, with a mean of 1.616 ± 0.217 μg/mL. There was no correlation between sensitivity to propamidine and sensitivity to dimethachlon or carbendazim. After treated with propamidine, mycelia were thinner with irregular distortion and more branches; cell wall became thicker with uneven distribution of cytoplasm than untreated control. In addition, sclerotia production, cell membrane permeability and oxalic acid content significantly decreased. On detached oilseed rape leaves, propamidine exhibited better control efficacy than carbendazim at the same concentration whether the leaves were inoculated with carbendazim-sensitive or resistant strains. All the results showed that propamidine exhibited strong antifungal activity and potential application in controlling S . sclerotiorum . Importantly, these data will provide more information on understanding the mode of action of propamidine against S . sclerotiorum and should be valuable for development of new antifungal drugs. [ABSTRACT FROM AUTHOR]

• In-silico based virtual screening of a library (Drug Central Database) containing 4199 FDA approved drugs; MM/GBSA and MD simulation analysis were performed. • Novel structurally modified propamidine derivatives were synthesized, characterized and tested for their anti-AD activity. • Compound 27 was a well-balanced and promising multi-targeting agent. • Compound 27 exhibited good self and AChE-induced Aβ aggregation inhibition in thioflavin T assay. • Compound 27 displayed significant improvement in cognitive dysfunctions against scopolamine-induced amnesia mouse models. The use of multifunctional agents could act as a crucial strategy in the management of neurodegenerative disorders like Alzheimer's disease (AD). In search of multitargeted directed ligands for the treatment of AD, a drug repositioning study has been performed using In silico tools. Virtual screening of a library (Drug Central Database) containing 4199 FDA-approved drugs was utilized for the purpose, and denopamine, guanethidine, and propamidine were identified as hits to target both acetylcholinesterase (AChE) and β-secretase (BACE-1). Further, MM/GBSA and MD simulation analysis was also performed which suggested that propamidine, an antibacterial and antifungal drug , may become a crucial pharmacophore to design multi-target directed ligands for AD therapy. Finally, a series of structurally modified derivatives of propamidine by replacement of terminal amidines with substituted benzamide and acetamide moiety on both ends were synthesized, characterized, and tested for their anti-AD action. Compound 27 of the structurally modified series of propamidine has shown significant in vitro hAChE and hBACE-1 inhibition at submicromolar concentration range (hAChE: IC 50 = 0.832 ± 0.05 µM and hBACE-1: IC 50 = 0.428 ± 0.036 µM). Compounds 27 has also shown significant propidium iodide displacement from the PAS binding region and exhibited good self and AChE-induced Amyloid-β (Aβ) aggregation inhibition in thioflavin T assay. The in-vivo behavioral studies of compound 27 displayed significant improvement in cognitive dysfunctions against scopolamine-induced amnesia mouse models. [Display omitted] [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose: To determine the in vitro drug susceptibility of Australian corneal isolates of Acanthamoeba and to correlate the results with patient treatment and visual outcome. Methods: Acanthamoeba isolates were obtained from a reference laboratory. Cyst suspensions were prepared from 19 strains and exposed to 10 antimicrobial agents for 7 days. The minimum drug concentrations required to inhibit excystation were determined. Inhibited cells were then plated out to determine minimum cysticidal concentrations. Results: Overall, propamidine proved to be the most active anti-Acanthamoeba agent tested. The disinfectant polyhexamethylene biguanide, either pure or in Baquacil, was also effective. Pentamidine, hexamidine, chlorhexidine and chloroxylenol had intermediate activity, while neomycin, amphotericin B and povidone-iodine had poor activity. There was no clear relationship between in vitro susceptibility and visual outcome. Conclusions: Propamidine and polyhexamethylene biguanide drops are recommended as initial choices for the treatment of Acanthamoeba keratitis. The variability in the susceptibility to any one agent suggests that individual testing of isolates is necessary to identify the most appropriate treatment. A number of factors influence visual outcome in these cases; further studies are required to resolve the importance or otherwise of in vitro susceptibility. [ABSTRACT FROM AUTHOR]

Purpose: To describe the outcome of a series ofAcanthamoeba keratitis treated with a similar regimen. Methods: All cases diagnosed with Acanthamoeba keratitisin a referral centre from June 1994 through June 1997 wereincluded. Diagnosis of Acanthamoeba keratitis was based inclinical presentation and laboratory results. Positive laboratoryidentification of Acanthamoeba from corneal scraping or contactlens was required, unless the patient had very characteristicsymptoms (severe pain) and signs of the infection, includingperineural infiltrates. Initial intensive treatment includedtopical polyhexamethylene biguanide (PHMB) 0.02%, propamidineisothionate 0.1% and broad-spectrum antibiotics. The treatmentwas gradually tapered. After documented response toanti-acanthamoeba therapy, topical steroids were introduced; theywere discontinued before cessation of the anti-Acanthamoebaregimen. Results: Six males and four females, with a meanage of 30.0 ± 7.4 years were included in this study. Allcases weared contact lenses. On presentation all cases had severepain, and epitheliopathy was associated with stromal infiltratein most (seven of ten) cases. Four patients had anterior uveitis.Perineural infiltrates were present in three cases and ringinfiltrate in one patient. Anti-amoebic treatment was started12.7 ± 7.2 days after beginning of symptoms. The clinicalresponse to therapy was very satisfactory in all patients. Withintwo to three weeks all patients had remarkable lessening of painand photophobia, and improvement of clinical signs. At two tothree months, visual acuity had improved in all patients. Twopatients required penetrating keratoplasty for visualrehabilitation. Conclusion: The use of PHMB and propamidinecured all cases of Acanthamoeba keratitis. Cautious introductionof steroids was associated with expedited resolution ofinflammation and provided symptomatic relief. [ABSTRACT FROM AUTHOR]

In the current study, a total of 53 isolates of Alternaria brassicicola collected from Shaanxi Province of China were characterized for their sensitivity to propamidine. The EC 50 (50% effective concentration) values for propamidine inhibiting mycelial growth and spore germination ranged from 0.515 to 3.247 µg/ml and 0.393 to 2.982 µg/ml, with average EC 50 values of 1.327 ± 0.198 µg/ml and 1.106 ± 0.113 µg/ml, respectively. In greenhouse experiments, propamidine at 100 µg/ml provided >90% efficacy against dark leaf spot on cabbage, which was higher than the efficacy obtained by azoxystrobin at the same concentration. After treatment with propamidine, fungal growth distortions were observed in the form of excess mycelial branching, thickened cell walls, decreased cell membrane permeability, and increased chitin content. Interestingly, colony color faded after treatment with propamidine compared with that of the untreated parental isolates. Importantly, the expressions of melanin biosynthesis-associated genes Amr1 , Scd1 , Brn1 , and Brn2 were downregulated at different levels. The obtained baseline sensitivity and control efficacy data suggested that propamidine inhibited not only growth of A. brassicicola but also melanin biosynthesis, which could reduce the biocompatibility of A. brassicicola in the field. These biological characteristics encourage further investigation of the mechanism of action of propamidine against A. brassicicola .

Background: We designed hybrid molecules between propamidine and benzimidazole in order to retain the antiprotozoal action, but decreasing the toxic effect of the molecule., Objective: Design and prepare 12 hybrids for testing their antiparasitic effect over three protozoa: Giardia intestinalis, Trichomonas vaginalis and Leishmania mexicana, as well as conduct several in silico simulations such as toxicological profile, molecular docking and molecular dynamics in order to understand their potential mode of action., Methods: Hybrids 1-3, 6-9 and 12 were obtained using a chemical pathway previously reported. Compounds 4, 5, 10 and 11 were prepared using a one-pot reduction-cyclization reaction. The in vitro antiparasitic and cytotoxic activities of these compounds were conducted. It was calculated several properties such as toxicity, PK behavior, as well as docking studies and molecular dynamics of the most active compound performed in a DNA sequence dodecamer in comparison with propamidine., Results: Compound 2 was 183, 127 and 202 times more active against G. intestinalis than metronidazole, pentamidine and propamidine. It was eleven times more active than pentamidine against L. mexicana. This compound showed low in vitro mammalian cytotoxicity. Molecular simulations showed a stable complex 2-DNA that occurred in the minor groove, analogous to propamidine-DNA complex., Conclusion: Compound 2, exhibited the higher bioactivity, especially towards G. intestinalis and L. mexicana. This study demonstrated that the replacement of benzimidazole scaffold instead of toxic amidine group in propamidine, results in an enhancement of antiprotozoal bioactivity. The preliminary molecular dynamics simulation suggests that the ligand-DNA complex is stable., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)