Modulation of Cyp450, ALS1 and COX-2 signaling pathways induced by Candida albicans infection via novel antifungal agents
Although, fluconazole is widely used in clinical treatment as an antifungal drug, it recorded potential problems as resistance and intracellular accumulation. Female albino mice were injected with single ip dose of Candida albicans (1.5 × 106 CFU). Three weeks post treatment with fluconazole and two...
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| Published in | Saudi pharmaceutical journal Vol. 26; no. 3; pp. 349 - 357 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
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Saudi Arabia
Elsevier B.V
01.03.2018
Elsevier |
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| Abstract | Although, fluconazole is widely used in clinical treatment as an antifungal drug, it recorded potential problems as resistance and intracellular accumulation. Female albino mice were injected with single ip dose of Candida albicans (1.5 × 106 CFU). Three weeks post treatment with fluconazole and two novel synthesized compounds [(2-(4-(Pyridin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridin-2-yl) pyridine-3carbonitrile) and (2-(4-(Pyrimidin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridine-2-yl)pyridine-3-carbonitrile) (13b & 14b, respectively)] in both low and high doses (50 mg/kg & 200 mg/kg), liver function and vaginal inflammation were assessed. Candida albicans significantly elevated serum alanine aminotransferase (ALT) and butrylcholinesterase (BCHE) as well as hepatic malondialdehyde (MDA). Molecular analysis confirmed a significant up-regulation in mRNA gene expression of Agglutinin-like sequence (ALS1), hepatic cytochrome p450 (Cyp450). Vaginal COX-2 gene expression was also elevated. Nevertheless, a significant down-regulation was apparent in mice treated with the aforementioned compounds. Meanwhile, administration of 14b in a high dose noticeably down-regulated the altered parameters expression showing a significant effect in comparison to animals treated with the variable doses of the tested compounds. Histopathological finding confirmed the obtained results. The current work investigated the efficiency of new synthetic pyrimidine derivatives 14bas anti-microbial agents and recommended to be improved and evaluated as a novel antifungal drug to overcome the emergence of resistance problem. |
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| AbstractList | Although, fluconazole is widely used in clinical treatment as an antifungal drug, it recorded potential problems as resistance and intracellular accumulation. Female albino mice were injected with single ip dose of Candida albicans (1.5 × 106 CFU). Three weeks post treatment with fluconazole and two novel synthesized compounds [(2-(4-(Pyridin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridin-2-yl) pyridine-3carbonitrile) and (2-(4-(Pyrimidin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridine-2-yl)pyridine-3-carbonitrile) (13b & 14b, respectively)] in both low and high doses (50 mg/kg & 200 mg/kg), liver function and vaginal inflammation were assessed. Candida albicans significantly elevated serum alanine aminotransferase (ALT) and butrylcholinesterase (BCHE) as well as hepatic malondialdehyde (MDA). Molecular analysis confirmed a significant up-regulation in mRNA gene expression of Agglutinin-like sequence (ALS1), hepatic cytochrome p450 (Cyp450). Vaginal COX-2 gene expression was also elevated. Nevertheless, a significant down-regulation was apparent in mice treated with the aforementioned compounds. Meanwhile, administration of 14b in a high dose noticeably down-regulated the altered parameters expression showing a significant effect in comparison to animals treated with the variable doses of the tested compounds. Histopathological finding confirmed the obtained results. The current work investigated the efficiency of new synthetic pyrimidine derivatives 14bas anti-microbial agents and recommended to be improved and evaluated as a novel antifungal drug to overcome the emergence of resistance problem. Although, fluconazole is widely used in clinical treatment as an antifungal drug, it recorded potential problems as resistance and intracellular accumulation. Female albino mice were injected with single dose of (1.5 × 10 CFU) Three weeks post treatment with fluconazole and two novel synthesized compounds [(2-(4-(Pyridin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridin-2-yl) pyridine-3carbonitrile) and (2-(4-(Pyrimidin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridine-2-yl)pyridine-3-carbonitrile) (13b & 14b, respectively)] in both low and high doses (50 mg/kg & 200 mg/kg), liver function and vaginal inflammation were assessed. significantly elevated serum alanine aminotransferase (ALT) and butrylcholinesterase (BCHE) as well as hepatic malondialdehyde (MDA). Molecular analysis confirmed a significant up-regulation in mRNA gene expression of Agglutinin-like sequence (ALS1), hepatic cytochrome p450 (Cyp450). Vaginal COX-2 gene expression was also elevated. Nevertheless, a significant down-regulation was apparent in mice treated with the aforementioned compounds. Meanwhile, administration of 14b in a high dose noticeably down-regulated the altered parameters expression showing a significant effect in comparison to animals treated with the variable doses of the tested compounds. Histopathological finding confirmed the obtained results. The current work investigated the efficiency of new synthetic pyrimidine derivatives 14bas anti-microbial agents and recommended to be improved and evaluated as a novel antifungal drug to overcome the emergence of resistance problem. Although, fluconazole is widely used in clinical treatment as an antifungal drug, it recorded potential problems as resistance and intracellular accumulation. Female albino mice were injected with single ip dose of Candida albicans (1.5 × 10 6 CFU) . Three weeks post treatment with fluconazole and two novel synthesized compounds [(2-(4-(Pyridin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridin-2-yl) pyridine-3carbonitrile) and (2-(4-(Pyrimidin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridine-2-yl)pyridine-3-carbonitrile) (13b & 14b, respectively)] in both low and high doses (50 mg/kg & 200 mg/kg), liver function and vaginal inflammation were assessed. Candida albicans significantly elevated serum alanine aminotransferase (ALT) and butrylcholinesterase (BCHE) as well as hepatic malondialdehyde (MDA). Molecular analysis confirmed a significant up-regulation in mRNA gene expression of Agglutinin-like sequence (ALS1), hepatic cytochrome p450 (Cyp450). Vaginal COX-2 gene expression was also elevated. Nevertheless, a significant down-regulation was apparent in mice treated with the aforementioned compounds. Meanwhile, administration of 14b in a high dose noticeably down-regulated the altered parameters expression showing a significant effect in comparison to animals treated with the variable doses of the tested compounds. Histopathological finding confirmed the obtained results. The current work investigated the efficiency of new synthetic pyrimidine derivatives 14bas anti-microbial agents and recommended to be improved and evaluated as a novel antifungal drug to overcome the emergence of resistance problem. |
| Author | Abood, Amira Abdel Megeed, Rehab M Kadry, Mai O Fayed, Dalia B. |
| AuthorAffiliation | a Molecular Biology, Therapeutic Chemistry Department, National Research Centre-Dokki, Cairo, Egypt c Microbiology, Chemistry of Natural and Microbial Products Department, National Research Centre-Dokki, Cairo, Egypt b Biochemistry, Therapeutic Chemistry Department, National Research Centre-Dokki, Cairo, Egypt |
| AuthorAffiliation_xml | – name: a Molecular Biology, Therapeutic Chemistry Department, National Research Centre-Dokki, Cairo, Egypt – name: c Microbiology, Chemistry of Natural and Microbial Products Department, National Research Centre-Dokki, Cairo, Egypt – name: b Biochemistry, Therapeutic Chemistry Department, National Research Centre-Dokki, Cairo, Egypt |
| Author_xml | – sequence: 1 givenname: Rehab M surname: Abdel Megeed fullname: Abdel Megeed, Rehab M email: rehabzenbaa@gmail.com organization: Molecular Biology, Therapeutic Chemistry Department, National Research Centre-Dokki, Cairo, Egypt – sequence: 2 givenname: Dalia B. surname: Fayed fullname: Fayed, Dalia B. email: dfayednrc@yahoo.com organization: Biochemistry, Therapeutic Chemistry Department, National Research Centre-Dokki, Cairo, Egypt – sequence: 3 givenname: Amira surname: Abood fullname: Abood, Amira email: dr.amiraabood@yahoo.com organization: Microbiology, Chemistry of Natural and Microbial Products Department, National Research Centre-Dokki, Cairo, Egypt – sequence: 4 givenname: Mai O surname: Kadry fullname: Kadry, Mai O email: maiosman666@yahoo.com organization: Biochemistry, Therapeutic Chemistry Department, National Research Centre-Dokki, Cairo, Egypt |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29556126$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1007_s12668_024_01361_9 crossref_primary_10_4155_tde_2023_0121 crossref_primary_10_1111_cts_12690 crossref_primary_10_1016_j_mycmed_2023_101437 |
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| Keywords | Candida albicans Fluconazole Cyp450 COX-2 ALS1 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Address: Chemistry of Natural and Microbial Products Department, National Research Centre, El Buhouth St., Dokki, Cairo, Egypt. Address: Therapeutic Chemistry Department, National Research Centre, El Buhouth St., Dokki, Cairo, Egypt. |
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| Title | Modulation of Cyp450, ALS1 and COX-2 signaling pathways induced by Candida albicans infection via novel antifungal agents |
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