Biological evaluation and pharmacokinetic profiling of a coumarin-benzothiazole hybrid as a new scaffold for human gliomas
A coumarin-benzothiazole hybrid 3 was recently reported as a potential anticancer lead compound based on antioxidant and α-glucosidase inhibitory activities. Herein, we report anticancer activity of the lead compound 3 at a single dose (10 μM) against a panel of 60 cancer cell lines. Analysis of the...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-09-01
|
| Series: | Medicine in Drug Discovery |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590098620300014 |
| _version_ | 1818506276629381120 |
|---|---|
| author | Moustafa T. Gabr Sefa Celik Sevim Akyuz Aysen E. Ozel |
| author_facet | Moustafa T. Gabr Sefa Celik Sevim Akyuz Aysen E. Ozel |
| author_sort | Moustafa T. Gabr |
| collection | DOAJ |
| description | A coumarin-benzothiazole hybrid 3 was recently reported as a potential anticancer lead compound based on antioxidant and α-glucosidase inhibitory activities. Herein, we report anticancer activity of the lead compound 3 at a single dose (10 μM) against a panel of 60 cancer cell lines. Analysis of the five-dose screening by NCI against 60 cancer cell lines is discussed as well. Investigation of the pharmacokinetic properties of the lead compound is presented in this study. The effect of the hybrid compound 3 on the viability of various human glioma cells and its ability to cross the blood brain barrier (BBB) in PAMPA-BBB assay were further investigated. The oxidative alterations caused by 3 in human glioma cells were determined using colorimetric measurements. In vitro and in vivo pharmacokinetic profiling of 3 support its potential as a candidate for further screening in animal models of gliomas. The drug likeness properties of 3 were further investigated by in silico assessment of its physicochemical properties and toxicity risks. Moreover, in silico studies were conducted for evaluation of ADMET of 3. The selective and potent anticancer activity of 3 as well as desirable pharmacokinetic properties renders 3 a promising lead for development of anticancer therapeutics. |
| first_indexed | 2024-12-10T22:02:23Z |
| format | Article |
| id | doaj.art-962e14f9732347a48ba643a3454e384e |
| institution | Directory Open Access Journal |
| issn | 2590-0986 |
| language | English |
| last_indexed | 2024-12-10T22:02:23Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Medicine in Drug Discovery |
| spelling | doaj.art-962e14f9732347a48ba643a3454e384e2022-12-22T01:31:51ZengElsevierMedicine in Drug Discovery2590-09862020-09-017100012Biological evaluation and pharmacokinetic profiling of a coumarin-benzothiazole hybrid as a new scaffold for human gliomasMoustafa T. Gabr0Sefa Celik1Sevim Akyuz2Aysen E. Ozel3Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; Corresponding author at: Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA.Physics Department, Science Faculty, Istanbul University, Vezneciler 34134, Istanbul, TurkeyPhysics Department, Science and Letters Faculty, Istanbul Kultur University, Atakoy Campus, Bakirkoy 34156, Istanbul, TurkeyPhysics Department, Science Faculty, Istanbul University, Vezneciler 34134, Istanbul, TurkeyA coumarin-benzothiazole hybrid 3 was recently reported as a potential anticancer lead compound based on antioxidant and α-glucosidase inhibitory activities. Herein, we report anticancer activity of the lead compound 3 at a single dose (10 μM) against a panel of 60 cancer cell lines. Analysis of the five-dose screening by NCI against 60 cancer cell lines is discussed as well. Investigation of the pharmacokinetic properties of the lead compound is presented in this study. The effect of the hybrid compound 3 on the viability of various human glioma cells and its ability to cross the blood brain barrier (BBB) in PAMPA-BBB assay were further investigated. The oxidative alterations caused by 3 in human glioma cells were determined using colorimetric measurements. In vitro and in vivo pharmacokinetic profiling of 3 support its potential as a candidate for further screening in animal models of gliomas. The drug likeness properties of 3 were further investigated by in silico assessment of its physicochemical properties and toxicity risks. Moreover, in silico studies were conducted for evaluation of ADMET of 3. The selective and potent anticancer activity of 3 as well as desirable pharmacokinetic properties renders 3 a promising lead for development of anticancer therapeutics.http://www.sciencedirect.com/science/article/pii/S2590098620300014Anticancer activityPharmacokineticADMETIn silicoHybridization |
| spellingShingle | Moustafa T. Gabr Sefa Celik Sevim Akyuz Aysen E. Ozel Biological evaluation and pharmacokinetic profiling of a coumarin-benzothiazole hybrid as a new scaffold for human gliomas Medicine in Drug Discovery Anticancer activity Pharmacokinetic ADMET In silico Hybridization |
| title | Biological evaluation and pharmacokinetic profiling of a coumarin-benzothiazole hybrid as a new scaffold for human gliomas |
| title_full | Biological evaluation and pharmacokinetic profiling of a coumarin-benzothiazole hybrid as a new scaffold for human gliomas |
| title_fullStr | Biological evaluation and pharmacokinetic profiling of a coumarin-benzothiazole hybrid as a new scaffold for human gliomas |
| title_full_unstemmed | Biological evaluation and pharmacokinetic profiling of a coumarin-benzothiazole hybrid as a new scaffold for human gliomas |
| title_short | Biological evaluation and pharmacokinetic profiling of a coumarin-benzothiazole hybrid as a new scaffold for human gliomas |
| title_sort | biological evaluation and pharmacokinetic profiling of a coumarin benzothiazole hybrid as a new scaffold for human gliomas |
| topic | Anticancer activity Pharmacokinetic ADMET In silico Hybridization |
| url | http://www.sciencedirect.com/science/article/pii/S2590098620300014 |
| work_keys_str_mv | AT moustafatgabr biologicalevaluationandpharmacokineticprofilingofacoumarinbenzothiazolehybridasanewscaffoldforhumangliomas AT sefacelik biologicalevaluationandpharmacokineticprofilingofacoumarinbenzothiazolehybridasanewscaffoldforhumangliomas AT sevimakyuz biologicalevaluationandpharmacokineticprofilingofacoumarinbenzothiazolehybridasanewscaffoldforhumangliomas AT ayseneozel biologicalevaluationandpharmacokineticprofilingofacoumarinbenzothiazolehybridasanewscaffoldforhumangliomas |