Pharmacological and Toxicological Screening of Novel Benzimidazole-Morpholine Derivatives as Dual-Acting Inhibitors

Can, Nafiz Öncü; Çevik, Ulviye Acar; Sağlık, Begüm Nurpelin; Özkay, Yusuf; Atlı, Özlem; Baysal, Merve; Özkay, Ümide Demir; Can, Özgür Devrim

doi:10.3390/molecules22081374

Cited by 19 publications

(8 citation statements)

References 55 publications

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“…The results of the present study did not show any significant increases in the frequencies of SCEs and MN in lymphocytes after exposure to all synthesized compounds as compared to the control values in all three dose treatments ( Table 2). The toxicological screening of novel benzimidazole-morpholine derivatives performed by Ames test showed that the synthesized compounds had no genotoxic effects, in accordance with our findings [32]. In contrast to our results, the previous studies conducted by in vitro cytochalasin-B micronucleus test on human lymphocytes revealed that thiabendazole, carbendazim, and mebendazole containing benzimidazole rings caused an increase in MN frequency in a dose-dependent manner [33].…”

Section: Resultssupporting

confidence: 90%

Anticancer and antiangiogenesis activities of novel synthesized 2-substitutedbenzimidazoles molecules

Güner¹,

Polatlı²,

Akkan³

et al. 2019

Turk J Chem

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In this study, novel 2-substituted benzimidazoles molecules having triazole, thiadiazole, and oxadiazole rings were synthesized and were evaluated by anticancer, antioxidant/oxidant status, genotoxicity, and antiangiogenesis assays.Anticancer activity of the compounds was determined by MTT (0.5, 5, and 50 µ g/mL) and lactate dehydrogenase (LDH) release assays against human prostate and breast cancer cells. Oxidative status of cells was elicited by total oxidative stress and total antioxidant capacity methods. Chick chorioallantoic membrane assay was used to evaluate the antiangiogenic activity. Genotoxicity was evaluated by the sister chromatid exchange (SCE) and micronucleus (MN) tests in lymphocyte cultured human blood. Our results showed that some of the compounds synthesized had significant antiproliferative activity against both cancer cell lines (between 4.54 ± 0.35 and 20.17 ± 3.15 µ g/mL), with higher inhibition of the breast cancer, and caused inhibition of LDH release with a linear correlation to MTT results. Moreover, the 5 µ g/mL dose of these molecules led to an increase in antioxidant levels. Compounds had antiangiogenic effectiveness in a dose-dependent manner. Additionally, all of the compounds did not affect SCE and MN levels compared to controls.In conclusion, these newly synthesized molecules can be a resource of new anticancer agents with their nongenotoxic, antiproliferative, and antiangiogenic properties.

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Section: Resultssupporting

confidence: 90%

Anticancer and antiangiogenesis activities of novel synthesized 2-substitutedbenzimidazoles molecules

Güner¹,

Polatlı²,

Akkan³

et al. 2019

Turk J Chem

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“…Each experiment in antifungal assay was performed twice. The details of the anticandidal assay were reported in our previous study [55].…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Antifungal Potential of Some Novel Benzimidazole-1,3,4-Oxadiazole Compounds

et al. 2019

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Discovery of novel anticandidal agents with clarified mechanisms of action, could be a rationalist approach against diverse pathogenic fungal strains due to the rise of resistance to existing drugs. In support to this hypothesis, in this paper, a series of benzimidazole-oxadiazole compounds were synthesized and subjected to antifungal activity evaluation. In vitro activity assays indicated that some of the compounds exhibited moderate to potent antifungal activities against tested Candida species when compared positive control amphotericin B and ketoconazole. The most active compounds 4h and 4p were evaluated in terms of inhibitory activity upon ergosterol biosynthesis by an LC-MS-MS method and it was determined that they inhibited ergosterol synthesis concentration dependently. Docking studies examining interactions between most active compounds and lanosterol 14-α-demethylase also supported the in vitro results.

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“…The in vitro antifungal activities of all resynthesized derivatives 4a-4o were screened at between 1 mg/mL-1.95 µg/mL concentrations using various Candida strains including C. albicans (ATCC 90030), C. glabrata (ATCC 90030) C. krusei (ATCC 6258) and C. parapsilopsis (ATCC 22019) and following the protocol of the EUCAST in keeping with the previous studies reported by our research group [21,22].…”

Section: Antifungal Activitymentioning

confidence: 99%

“…According to the protocol of the EUCAST reported previously by our research group [21,22], all obtained compounds 4a-4o were screened for their in vitro antifungal activity against four pathogenic fungi;…”

Section: Antifungal Activitymentioning

confidence: 99%

Antifungal Activity of Some Benzimidazole-Hydrazones

Osmaniye

Çevik

2019

Cumhuriyet Science Journal

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In the present work, 15 4-(1-(prop-2-in-1-yl)-1H-benzoimidazole-2-yl)-N'-(substitutedmethylene)benzohydrazide derivatives (4a-4o) were re-synthesized to evaluate their antifungal activity. Structure identification of synthesized compounds was elucidated by 1 H-NMR, 13 C-NMR, and HRMS spectroscopic methods. Inhibitory potential of the re-synthesized compounds was investigated against Candida supp. The compounds 4e and 4l showed significant anti fungal activity. Consistent with the activity studies, 4e was found to be potent derivative with its MIC50 value of (1.95 µg/mL) against Candida glabrata. And 4l was found to be potent derivative with its MIC50 value of (1.95 µg/mL) against Candida krusei.Özet. Mevcut çalışmada, 15 4-(1-(prop-2-in-1-il)-1H-benzimidazol-2-il)-N'-(sübstitüemetilen) benzohidrazit türevleri (4a-4o), antifungal aktivitelerini değerlendirmek üzere yeniden sentezlendi. Sentezlenen bileşiklerin yapı tanımlamaları 1 H-NMR, 13 C-NMR ve HRMS spektroskopik yöntemlerle açıklandı. Yeniden sentezlenen bileşiklerin antifungal etkinlikleri Candida türlerine karşı değerlendirildi. Bileşik 4e ve 4l önemli aktivite gösterdi. Aktivite çalışmaları ile uyumlu olarak, 4e bileşiği Candida glabrata'ya karşı 1.95 µg / mL MIC50 değeri ile güçlü bir türev olarak bulundu. Aynı zamanda 4l bileşiği Candida krusei'ye karşı 1.95 µg / mL MIC50 değeri ile güçlü bir türev olarak bulundu.

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Pharmacological and Toxicological Screening of Novel Benzimidazole-Morpholine Derivatives as Dual-Acting Inhibitors

Cited by 19 publications

References 55 publications

Anticancer and antiangiogenesis activities of novel synthesized 2-substitutedbenzimidazoles molecules

Anticancer and antiangiogenesis activities of novel synthesized 2-substitutedbenzimidazoles molecules

Synthesis and Antifungal Potential of Some Novel Benzimidazole-1,3,4-Oxadiazole Compounds

Antifungal Activity of Some Benzimidazole-Hydrazones

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