Synthesis and In-Vivo Evaluation of Benzoxazole Derivatives as Promising Anti-Psoriatic Drugs for Clinical Use

被引:3
|
作者
Ayoub, Rami [1 ]
Jilani, Jamal [2 ]
Jarrar, Qais [1 ]
Alani, Raad [3 ]
Ardianto, Chrismawan [4 ]
Goh, Khang Wen [5 ]
Ali, Dalia [3 ]
Moshawih, Said [6 ]
机构
[1] Isra Univ, Fac Pharm, Dept Appl Pharmaceut Sci & Clin Pharm, Amman 11622, Jordan
[2] Jordan Univ Sci & Technol, Fac Pharm, Dept Med Chem & Pharmacognosy, Irbid 22110, Jordan
[3] Isra Univ, Fac Allied Med Sci, Dept Physiotherapy, Amman 11622, Jordan
[4] Univ Airlangga, Fac Pharm, Dept Pharm Practice, Surabaya 60115, Indonesia
[5] INTI Int Univ, Fac Data Sci & Informat Technol, Nilai 71800, Negeri Sembilan, Malaysia
[6] Univ Brunei Darussalam, PAP Rashidah Saadatul Bolkiah Inst Hlth Sci, Gadong 1410, Brunei
来源
MOLECULES | 2022年 / 27卷 / 09期
关键词
synthesis; arylbenzoxazole; psoriasis; imiquimod; in vivo; prodrug; SKIN INFLAMMATION; PSORIASIS; IMMUNOPATHOGENESIS; BENZOTHIAZOLE; AUTOIMMUNE;
D O I
10.3390/molecules27093023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
2-(4-Chlorophenyl)-5-benzoxazoleacetic acid (CBA) and its ester, methyl-2-(4-chloro-phenyl)-5-benzoxazoleacetate (MCBA), were synthesized, and their structures were confirmed by (HNMR)-H-1, IR, and mass spectrophotometry. The anti-psoriatic activities of CBA and MCBA were tested using an imiquimod (IMQ)-induced psoriatic mouse model, in which mice were treated both topically (1% w/w) and orally (125 mg/kg) for 14 days. The erythema intensity, thickness, and desquamation of psoriasis were scored by calculating the psoriasis area severity index (PASI). The study also included the determination of histopathological alterations in the skin tissues of treated mice. Topical and oral administration of CBA and MCBA led to a reduction in erythema intensity, thickness, and desquamation, which was demonstrated by a significant decrease in the PASI value. In addition, skin tissues of mice treated with CBA and MCBA showed less evidence of psoriatic alterations, such as hyperkeratosis, parakeratosis, scale crust, edema, psoriasiform, and hyperplasia. After administration of either topical or oral dosing, the anti-psoriatic effects were found to be stronger in MCBA-treated than in CBA-treated mice. These effects were comparable to those produced by Clobetasol propionate, the reference drug. This drug discovery could be translated into a potential new drug for future clinical use in psoriasis treatment.
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页数:12
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