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Relationships between the anthelmintic activity of eight derivatives of benzimidazole carbamates against Trichinella spiralis and their chemical structures

Latif LA, Surin J

Jpn. J. Med. Sci. Biol., 1993 Oct-Dec;46(5-6):203-14.
PMID: 8051807

Efficacy of eight recently developed and used anthelmintics of the benzimidazole carbamates; mebendazole, flubendazole, oxfendazole, albendazole, oxibendazole, 790163 proflubendazole, 780118 "cyanide" benzimidazole and 780120 "selenium" benzimidazole was tested orally against the enteral immature larval and adult stages of Trichinella spiralis in mice. Six of these derivatives of methyl benzimidazole-2-carbamates have an aryl and two have an alkyl substituent at the 5'-position of the parent benzimidazole ring. The nature of these substituents was found to be related to the antitrichinellous activity of the compounds. Compounds with the 5'-substituent linked to the parent benzimidazole ring by either a carbon, sulfur or an oxygen atom are more potent than those bridged by selenium or by the carbon with an attached-CN group. The result clearly indicates that the benzimidazoles are invariably more potent against immature enteral phase than the adult worms. This finding would be of importance in a targeted synthesis of new, effective derivatives of benzimidazole, e.g., in the screening for more important tissue-dwelling nematodes like filarial worms.

Matched MeSH terms: Carbamates/pharmacology*
Adulticide Resistance Status of Aedes albopictus (Diptera: Culicidae) in Sabah, Malaysia: A Statewide Assessment

Elia-Amira NMR, Chen CD, Low VL, Lau KW, Haziqah-Rashid A, Amelia-Yap ZH, et al.

J Med Entomol, 2019 10 28;56(6):1715-1725.
PMID: 31290534 DOI: 10.1093/jme/tjz117

Resistance status of Aedes albopictus (Diptera: Culicidae) collected from Sabah, East Malaysia, was evaluated against four major classes of adulticides, namely pyrethroid, carbamate, organochlorine, and organophosphate. Adult bioassays conforming to WHO standard protocols were conducted to assess knockdown and mortality rates of Ae. albopictus. Among tested pyrethroid adulticides, only cyfluthrin, lambda-cyaholthrin, and deltamethrin were able to inflict total knockdown. The other adulticide classes mostly failed to cause any knockdown; the highest knockdown rate was only 18.33% for propoxur. With regards to mortality rate, Ae. albopictus was unanimously susceptible toward all pyrethroids, dieldrin, and malathion, but exhibited resistance toward bendiocarb, propoxur, dichlorodiphenyltrichloroethane, and fenitrothion. Additionally, correlation analysis demonstrated cross-resistance between bendiocarb and propoxur, and malathion and propoxur. In conclusion, this study has disclosed that pyrethroids are still generally effective for Aedes control in Sabah, Malaysia. The susceptibility status of Ae. albopictus against pyrethroids in descending order was cyfluthrin > lambda-cyhalothrin > deltamethrin > etofenprox > permethrin.

Matched MeSH terms: Carbamates/pharmacology
Design, synthesis and biological evaluation of novel carbamates as potential inhibitors of acetylcholinesterase and butyrylcholinesterase

Wu J, Pistolozzi M, Liu S, Tan W

Bioorg Med Chem, 2020 03 01;28(5):115324.
PMID: 32008882 DOI: 10.1016/j.bmc.2020.115324

Rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), has been approved by U.S. Food and Drug Administration to treat Alzheimer's disease (AD) and Parkinson's disease (PD) dementia. In the current work, a bambuterol derivative lacking one of the carbamoyloxy groups on the benzene ring (BMC-1) and its analogues were synthesized using 1-(3-hydroxyphenyl) ethan-1-one and 1-(4-hydroxyphenyl) ethan-1-one as starting materials. In-vitro cholinesterase assay established that nine compounds were more potent to inhibit both electric eel AChE and equine serum BChE than rivastigmine under the same experimental conditions. Further study confirmed that among the nine carbamates, BMC-3 (IC50(AChE) = 792 nM, IC50(BChE) = 2.2 nM) and BMC-16 (IC50(AChE) = 266 nM, IC50(BChE) = 10.6 nM) were excellent cholinesterase inhibitors with potential of permeating through the blood-brain barrier. These carbamates could be used as potential dual inhibitors of AChE and BChE and to discover novel drugs for the treatment of AD and PD dementia.

Matched MeSH terms: Carbamates/pharmacology*
Insecticide susceptibility status of field-collected Aedes (Stegomyia) aegypti (L.) at a dengue endemic site in Shah Alam, Selangor, Malaysia

Rong LS, Ann AT, Ahmad NW, Lim LH, Azirun MS

Southeast Asian J Trop Med Public Health, 2012 Jan;43(1):34-47.
PMID: 23082552

Biweekly ovitrap surveillance (OS) was conducted for a year (August 2007 - September 2008) at two different dengue endemic sites in Shah Alam, Selangor, Malaysia, 50 km from Kuala Lumpur. Aedes aegypti collected from these 2 locations were raised to the F3 stage and subjected to a WHO standard bioassay method to determine lethal time (LT) against pyrethroids (permethrin 0.75%, cyfluthrin 0.15%), organophosphates (malathion 5.0%, fenitrothion 1.0%), carbamates (propoxur 0.1%, bendiocarb 0.1%) and organochlorine (DDT 4.0%). Insecticide susceptibilities were analyzed for one year. Aedes aegypti were resistant to DDT with a mortality range of 0 - 13.3% throughout the year at both sites. Susceptibilities to pyrethroids and carbamates varied throughout the year. In contrast, susceptibilities to pyrethroids and carbamates varied throughout the year: resistant to propoxur, bendiocarb and permethrin with mortality of < 80% in most months; but, showed incipient resistant to cyfluthrin in most months. Mosquitoes were consistently susceptible to malathion and fenitrothion, with complete mortality during most months. They were especially susceptible to malathion with LT50 values of 21.32 - 36.37 minutes, suggesting effectiveness of malathion for control of dengue.

Matched MeSH terms: Carbamates/pharmacology
Fulltext Antidiabetic Drugs and Their Nanoconjugates Repurposed as Novel Antimicrobial Agents against Acanthamoeba castellanii

Anwar A, Siddiqui R, Raza Shah M, Khan NA

J Microbiol Biotechnol, 2019 May 28;29(5):713-720.
PMID: 31030451 DOI: 10.4014/jmb/1903.03009

Acanthamoeba castellanii belonging to the T4 genotype may cause a fatal brain infection known as granulomatous amoebic encephalitis, and the vision-threatening eye infection Acanthamoeba keratitis. The aim of this study was to evaluate the antiamoebic effects of three clinically available antidiabetic drugs, Glimepiride, Vildagliptin and Repaglinide, against A. castellanii belonging to the T4 genotype. Furthermore, we attempted to conjugate these drugs with silver nanoparticles (AgNPs) to enhance their antiamoebic effects. Amoebicidal, encystation, excystation, and host cell cytotoxicity assays were performed to unravel any antiacanthamoebic effects. Vildagliptin conjugated silver nanoparticles (Vgt-AgNPs) characterized by spectroscopic techniques and atomic force microscopy were synthesized. All three drugs showed antiamoebic effects against A. castellanii and significantly blocked the encystation. These drugs also showed significant cysticidal effects and reduced host cell cytotoxicity caused by A. castellanii. Moreover, Vildagliptin-coated silver nanoparticles were successfully synthesized and are shown to enhance its antiacanthamoebic potency at significantly reduced concentration. The repurposed application of the tested antidiabetic drugs and their nanoparticles against free-living amoeba such as Acanthamoeba castellanii described here is a novel outcome that holds tremendous potential for future applications against devastating infection.

Matched MeSH terms: Carbamates/pharmacology
Optimization of an efficient semi-solid culture protocol for sterilization and plant regeneration of Centella asiatica (L.) as a medicinal herb

Moghaddam SS, Jaafar HB, Aziz MA, Ibrahim R, Rahmat AB, Philip E

Molecules, 2011;16(11):8981-91.
PMID: 22439138

The present study investigates the effects of different concentrations, as well as type of plant growth regulators (PGRs) and medium (MS, Duchefa) on the growth and development of Centella asiatica in semi-solid culture. In addition, a protocol for successful sterilization of C.asiatica explants prepared from field-grown plants highly exposed to fungal and bacterial contamination was determined. Results for sterilization treatments revealed that applying HgCl₂ and Plant Preservative Mixture (PPM) with cetrimide, bavistin and trimethoprim which were included after washing with tap water, followed by the addition of PPM in the medium, produced a very satisfactory result (clean culture 90 ± 1.33%) and TS5 (decon + cetrimide 1% + bavistin 150 mg/L + trimethoprim 50 mg/L + HgCl₂0.1% + PPM 2% soak and 2 mL/L in medium) was hence chosen as the best method of sterilization for C.asiatica. The synergistic combination of 6 benzylaminopurine (BAP) and 1-naphthaleneacetic acid (NAA) in concentrations of 2 mg/L and 0.1 mg/L, respectively, in Duchefa medium compared with MS induced the most optimal percentage of sprouted shoots (93 ± 0.667), number of shoots (5.2 ± 0.079) and nodes (4 ± 0.067) per explant, leaf per explant (14 ± 0.107) and shoot length (4.1 ± 0.67 cm). Furthermore, optimum rooting frequency (95.2 ± 0.81%), the number of roots/shoot (7.5 ± 0.107) and the mean root length (4.5 ± 0.133 cm) occurred for shoots that were cultured on full-strength MS medium containing 0.5 mg/L indole-3-butyric acid (IBA). In this study, the acclimatized plantlets were successfully established with almost 85% survival. The findings of this study have proven an efficient medium and PGR concentration for the mass propagation of C.asiatica. These findings would be useful in micropropagation and ex situ conservation of this plant.

Matched MeSH terms: Carbamates/pharmacology
CYP3A4 genetic polymorphism influences repaglinide's pharmacokinetics

Ruzilawati AB, Gan SH

Pharmacology, 2010;85(6):357-64.
PMID: 20523106 DOI: 10.1159/000302731

AIM: To investigate the effects of CYP3A4 and CYP2C8 enzymes on repaglinide's pharmacokinetics in healthy Malaysian subjects.
METHODS: Subjects (n = 121) received oral repaglinide (4 mg). Blood samples were taken at 0, 30, 60, 120, 180 and 240 min and serum concentrations of repaglinide were determined using high-performance liquid chromatography. Subjects were also genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for CYP3A4*4, *5 and*18 and by an allele-specific multiplex PCR for CYP2C8*2, *3, *4 and *5 alleles.
RESULTS: The allele frequencies of CYP2C8*1, *2, *3, *4 and *5 were 95.04, 0.40, 0.40, 0 and 4.13%, respectively. The frequencies of the CYP3A4*1, *4, *5 and *18 alleles were 97.93, 0, 0 and 2.07%, respectively. CYP2C8 and CYP3A4 genotypes were not significantly associated with repaglinide's blood glucose-lowering effect. However, the CYP3A4 genotype significantly influenced some of repaglinide's pharmacokinetics, where the mean elimination rate constant was 44.0% lower (p = 0.04) and the mean half-life was 33.8% higher (p = 0.04) in subjects with the CYP3A4*1/*18 genotype as compared to those with the normal CYP3A4*1/*1 genotype. This result confirms that CYP3A4 plays a large role in metabolizing repaglinide.
CONCLUSION: Genetic polymorphisms of CYP3A4, specifically CYP3A4*18, play a major role in contributing to the interindividual variability in repaglinide's pharmacokinetics.

Matched MeSH terms: Carbamates/pharmacology
Fulltext An open label comparative study of glimepiride versus repaglinide in type 2 diabetes mellitus Muslim subjects during the month of Ramadan

Anwar A, Azmi KN, Hamidon BB, Khalid BA

Med J Malaysia, 2006 Mar;61(1):28-35.
PMID: 16708731 MyJurnal

This study was conducted to compare the treatment efficacy between a prandial glucose regulator, repaglinide and a new sulphonylurea, glimepiride in Muslim Type 2 diabetic patients who practice Ramadan fasting. Forty-one patients, previously treated with a sulphonylurea or metformin, were divided to receive either repaglinide (n=20, preprandially three-times daily) or glimepiride (n=21, preprandially once daily) 3 months before the month of Ramadan. During Ramadan, patients modified their eating pattern to two meals daily, and the triple doses of repaglinide were redistributed to two preprandial doses. Four point blood glucose monitoring were performed weekly during the month of Ramadan and the subsequent month. Measurements of the 4-point blood glucose were significantly lower in the glimepiride group compared to the repaglinide group both during and after Ramadan. The glycaemic excursion was better in the morning for the repaglinide group and better in the afternoon and evening for the glimepiride group during the Ramadan period. There was no statistically significant difference in the incidence of hypoglycaemia between the two groups during and after Ramadan. There was no difference in the glycaemic excursion post-Ramadan. The longer duration of action of glimepiride may offer an advantage over repaglinide during the 13.5 hours of fast in Ramadan for diabetic patients.

Matched MeSH terms: Carbamates/pharmacology
Development of anti-acanthamoebic approaches

Mungroo MR, Tong T, Khan NA, Anuar TS, Maciver SK, Siddiqui R

Int Microbiol, 2021 Aug;24(3):363-371.
PMID: 33754231 DOI: 10.1007/s10123-021-00171-3

Acanthamoeba keratitis is a sight-endangering eye infection, and causative organism Acanthamoeba presents a significant concern to public health, given escalation of contact lens wearers. Contemporary therapy is burdensome, necessitating prompt diagnosis and aggressive treatment. None of the contact lens disinfectants (local and international) can eradicate Acanthamoeba effectively. Using a range of compounds targeting cellulose, ion channels, and biochemical pathways, we employed bioassay-guided testing to determine their anti-amoebic effects. The results indicated that acarbose, indaziflam, terbuthylazine, glimepiride, inositol, vildagliptin and repaglinide showed anti-amoebic effects. Compounds showed minimal toxicity on human cells. Therefore, effects of the evaluated compounds after conjugation with nanoparticles should certainly be the subject of future studies and will likely lead to promising leads for potential applications.

Matched MeSH terms: Carbamates/pharmacology
Synthesis and anticancer activity of novel water soluble benzimidazole carbamates

Cheong JE, Zaffagni M, Chung I, Xu Y, Wang Y, Jernigan FE, et al.

Eur J Med Chem, 2018 Jan 20;144:372-385.
PMID: 29288939 DOI: 10.1016/j.ejmech.2017.11.037

Metastases account for more than 90% of all cancer deaths and respond poorly to most therapies. There remains an urgent need for new therapeutic modalities for the treatment of advanced metastatic cancers. The benzimidazole methylcarbamate drugs, commonly used as anti-helmitics, have been suggested to have anticancer activity, but progress has been stalled by their poor water solubility and poor suitability for systemic delivery to disseminated cancers. We synthesized and characterized the anticancer activity of novel benzimidazoles containing an oxetane or an amine group to enhance solubility. Among them, the novel oxetanyl substituted compound 18 demonstrated significant cytotoxicity toward a variety of cancer cell types including prostate, lung, and ovarian cancers with strong activity toward highly aggressive cancer lines (IC50: 0.9-3.8 μM). Compound 18 achieved aqueous solubility of 361 μM. In a mouse xenograft model of a highly metastatic human prostate cancer, compound 18 (30 mg/kg) significantly inhibited the growth of established tumors (T/C: 0.36) without noticeable toxicity.

Matched MeSH terms: Carbamates/pharmacology*