Chlorquinaldol Research Articles

Chlorquinaldol inhibits the activation of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 inflammasome and ameliorates imiquimod-induced psoriasis-like dermatitis in mice

Psoriasis is a common chronic autoinflammatory/autoimmune skin disease associated with elevated pro-inflammatory cytokines. The pivotal role of interleukin (IL)-1β and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome in the pathogenesis of psoriasis has been widely described. Accordingly, the suppression of NLRP3-dependent IL-1β release is a potential therapy for psoriasis. Repurposing marketed drugs is a strategy for identifying new inhibitors of NLRP3 inflammasome activation. Herein, chlorquinaldol (CQD), a historic antimicrobial agent used as a topical treatment for skin and vaginal infections, was found to have a distinct effect by inhibiting NLRP3 inflammasome activation at concentrations ranging from 2 to 6 μM. CQD significantly suppressed apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) oligomerization, NLRP3-ASC interaction, and pyroptosis in macrophages. The levels of cleaved IL-1β and caspase-1 were reduced by CQD in the cell lysates of macrophages, suggesting that CQD acted on upstream of pore formation in the cell membrane. Mechanistically, CQD reduced mitochondrial reactive oxygen species production but did not affect the nuclear factor-κB (NF-κB) pathway. Intraperitoneal administration of CQD (15 mg/kg) for 6 days was found to improve the skin lesions in the imiquimod-induced psoriatic mouse model (male C57BL/6 mice), while secretion of pro-inflammatory cytokines (IL-17 and IL-1β) and keratinocyte proliferation were significantly suppressed by CQD. In conclusion, CQD exerted inhibitory effects on NLRP3 inflammasome activation in macrophages and decreased the severity of psoriatic response in vivo. Such findings indicate that the repurposing of the old drug, CQD, is a potential pharmacological approach for the treatment of psoriasis and other NLRP3-driven diseases.

Liquid chromatographic and spectrophotometric determination of diflucortolone valerate and chlorquinaldol in creams

A new reversed phase high pressure liquid chromatography and a spectrophotometric method are proposed for the simultaneous determination of diflucortolone valerate (DIF) and chlorquinaldol (CHL) in creams. An isocratic system consisted of an ACE® C18 analytical column and a mobile phase composed of methanol/phosphate buffer (pH 5.5, 0.1 M) (95:5, v/v) at a flow rate 1.0 mL/min was used for the optimal chromatographic separation using UV detection at 220 nm. Ephedrine hydrochloride was used as internal standard. Principal component regression (PCR) was used as the chemometric technique in spectrophotometry. In this technique, the concentration data matrix was prepared by using the synthetic mixtures containing these drugs in methanol/water (3:1). The absorbance data matrix corresponding to the concentration data matrix was obtained by measuring the absorbances at 60 wavelengths in the range of 230-348 nm with appropriate interval Δλ of 2 nm for DIF and CHL in the zero-order spectra for the binary combinations. The linear ranges were found 2.40-300 μg/mL for DIF, 0.72-240 μg/mL for CHL for LC method, and 0.88-3.0 μg/mL for DIF and 1.0-11.2 μg/mL for CHL for PCR method. The accuracy, precision and the linear ranges of the methods have been evaluated and they have been validated by analyzing synthetic mixtures containing the title drugs. These two methods were successfully applied to two pharmaceutical cream preparations and the results were compared with each other.

Chlorquinaldol targets the β-catenin and T-cell factor 4 complex and exerts anti-colorectal cancer activity

Aberrant activation of Wnt signaling plays a critical role in the initiation and progression of colorectal cancer (CRC). Chlorquinaldol (CQD) is a topical antimicrobial agent used to treat skin infections. Little is known about the anticancer activity of CQD and its underlying mechanisms. In this study, CQD was demonstrated to inhibit Wnt/β-catenin signaling through targeting the downstream part of this pathway. The results showed that CQD could inhibit the acetylation of β-catenin and disrupt the interaction of β-catenin with T-cell factor 4 (TCF4), leading to reduced binding of β-catenin to the promoters of Wnt target genes and downregulation of the expression of these target genes. Moreover, treatment with CQD suppressed the proliferation, migration, invasion and stemness of CRC cells. In APCmin/+ mice and CRC cell xenografts, administration of CQD suppressed tumor growth and the expression of Wnt target genes c-Myc and Leucine-rich G protein-coupled receptor-5 (LGR5). These results strongly suggest that CQD may be a promising therapeutic agent in the treatment of CRC.

Comparative Study of the Resolution Efficiency of High-performance Liquid Chromatographic and Chemometrics-assisted UV Spectrophotometric Methods: Application on Pharmaceutical Mixtures

High-performance liquid chromatographic and two chemometrics-assisted UV spectrophotometric methods were proposed for the resolution of pharmaceutical binary mixtures of lidocaine hydrochloride(LH) and fluocortolone pivalate, (FCP) and their ternary mixture with chlorquinaldol (CQ) without any chemical pretreatment. The chromatographic separation was achieved on normal-phase C8 analytical column with a mobile phase consisting of a mixture of phosphate buffer : acetonitrile (40:60, v/v) buffered with 0.5% triethylamine, (adjusted to pH 3.3 ± 0.2 with o- phosphoric acid) with flow rate 1 mL/min. Quantitation was achieved with UV detection at 220 nm. Also, the resolution has been accomplished by using numerical spectrophotometric methods as principal component regression (PCR) and partial least squares (PLS-1) applied to the UV spectra of the mixture. The proposed methods were validated and successfully applied for the analysis of dosage forms and laboratory-prepared mixtures containing the components combination. The developed analytical methods did not show any interference of the excipients when applied to pharmaceutical dosage forms. The results of HPLC were compared with PLS-1 and PCR methods and a good agreement was found.

A comparative study of novel spectrophotometric resolution techniques applied for pharmaceutical mixtures with partially or severely overlapped spectra

Simultaneous determination of mixtures of lidocaine hydrochloride (LH), flucortolone pivalate (FCP), in presence of chlorquinaldol (CQ) without prior separation steps was applied using either successive or progressive resolution techniques. According to the concentration of CQ the extent of overlapping changed so it can be eliminated from the mixture to get the binary mixture of LH and FCP using ratio subtraction method for partially overlapped spectra or constant value via amplitude difference followed by ratio subtraction or constant center followed by spectrum subtraction spectrum subtraction for severely overlapped spectra. Successive ratio subtraction was coupled with extended ratio subtraction, constant multiplication, derivative subtraction coupled constant multiplication, and spectrum subtraction can be applied for the analysis of partially overlapped spectra. On the other hand severely overlapped spectra can be analyzed by constant center and the novel methods namely differential dual wavelength (D1 DWL) for CQ, ratio difference and differential derivative ratio (D1 DR) for FCP, while LH was determined by applying constant value via amplitude difference followed by successive ratio subtraction, and successive derivative subtraction. The spectra of the cited drugs can be resolved and their concentrations are determined progressively from the same ratio spectrum using amplitude modulation method. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures and were successfully applied for the analysis of pharmaceutical formulations containing the cited drugs with no interference from additives. The proposed methods were validated according to the ICH guidelines. The obtained results were statistically compared with those of the official or reported methods; using student t-test, F-test, and one way ANOVA, showing no significant difference with respect to accuracy and precision.

Spectrofluorimetric flow-injection method for the successive determination of chloroxine and chlorquinaldol in pharmaceutical preparations

A flow-injection method is proposed for the sequential determination of chloroxine (COX) and chlorquinaldol (CQD) at sub-μ ml −1 levels in mixtures. The method is based on the different behaviour of these analytes with metal ions. Aluminum(III) only reacts with COX to form a fluorescent complex, whereas cadmium(II) reacts with both analytes forming fluorescent complexes. The use of two sub-systems, through which aluminum or cadmium are pumped, makes it possible to obtain analytical signals due to the contributions of COX or COX plus CQD, respectively. The features of the method (linearity in the range 0.1–13 μg ml −1 RSD smaller than 2.5% in all instances and sampling frequency 30 h −1) and the results obtained on application to pharmaceutical preparations show its usefulness.