Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal Model
In this study, we synthesized benzodioxol carboxamide derivatives and investigated their antidiabetic potential. The synthesized compounds (<b>Ia-Ic</b> and <b>IIa-IId</b>) underwent characterization via HRMS, <sup>1</sup>H-, <sup>13</sup>CAPT-NMR, and...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/13/10/1486 |
| _version_ | 1797574525350576128 |
|---|---|
| author | Mohammed Hawash Derar Al-Smadi Anil Kumar Barbara Olech Paulina Maria Dominiak Nidal Jaradat Sarah Antari Sarah Mohammed Ala’a Nasasrh Murad Abualhasan Ahmed Musa Shorooq Suboh İrfan Çapan Mohammad Qneibi Hiba Natsheh |
| author_facet | Mohammed Hawash Derar Al-Smadi Anil Kumar Barbara Olech Paulina Maria Dominiak Nidal Jaradat Sarah Antari Sarah Mohammed Ala’a Nasasrh Murad Abualhasan Ahmed Musa Shorooq Suboh İrfan Çapan Mohammad Qneibi Hiba Natsheh |
| author_sort | Mohammed Hawash |
| collection | DOAJ |
| description | In this study, we synthesized benzodioxol carboxamide derivatives and investigated their antidiabetic potential. The synthesized compounds (<b>Ia-Ic</b> and <b>IIa-IId</b>) underwent characterization via HRMS, <sup>1</sup>H-, <sup>13</sup>CAPT-NMR, and MicroED. Their efficacy against α-amylase was assessed in vitro, while MTS assays were employed to gauge cytotoxicity across cancer and normal cell lines. Additionally, the antidiabetic impact of compound <b>IIc</b> was evaluated in vivo using a streptozotocin-induced diabetic mice model. Notably, <b>IIa</b> and <b>IIc</b> displayed potent α-amylase inhibition (IC<sub>50</sub> values of 0.85 and 0.68 µM, respectively) while exhibiting a negligible effect on the Hek293t normal cell line (IC<sub>50</sub> > 150 µM), suggesting their safety. Compound <b>IId</b> demonstrated significant activity against four cancer cell lines (26–65 µM). In vivo experiments revealed that five doses of <b>IIc</b> substantially reduced mice blood glucose levels from 252.2 mg/dL to 173.8 mg/dL in contrast to the control group. The compelling in vitro anticancer efficacy of <b>IIc</b> and its safety for normal cells underscores the need for further in vivo assessment of this promising compound. This research highlights the potential of benzodioxol derivatives as candidates for the future development of synthetic antidiabetic drugs. |
| first_indexed | 2024-03-10T21:24:40Z |
| format | Article |
| id | doaj.art-9c58b669f4324401ac695c2786f37d07 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T21:24:40Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-9c58b669f4324401ac695c2786f37d072023-11-19T15:49:55ZengMDPI AGBiomolecules2218-273X2023-10-011310148610.3390/biom13101486Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal ModelMohammed Hawash0Derar Al-Smadi1Anil Kumar2Barbara Olech3Paulina Maria Dominiak4Nidal Jaradat5Sarah Antari6Sarah Mohammed7Ala’a Nasasrh8Murad Abualhasan9Ahmed Musa10Shorooq Suboh11İrfan Çapan12Mohammad Qneibi13Hiba Natsheh14Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, PalestineDepartment of Chemistry, Faculty of Sciences, An-Najah National University, Nablus 00970, PalestineBiological and Chemical Research Centre, Department of Chemistry, University of Warsaw, ul. Żwirki i Wigury 101, 02-089 Warsaw, PolandBiological and Chemical Research Centre, Department of Chemistry, University of Warsaw, ul. Żwirki i Wigury 101, 02-089 Warsaw, PolandBiological and Chemical Research Centre, Department of Chemistry, University of Warsaw, ul. Żwirki i Wigury 101, 02-089 Warsaw, PolandDepartment of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, PalestineDepartment of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, PalestineDepartment of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, PalestineDepartment of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, PalestineDepartment of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, PalestineDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, PalestineDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, PalestineDepartment of Material and Material Processing Technologies, Technical Sciences Vocational College, Gazi University, 06560 Ankara, TurkeyDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, PalestineDepartment of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, PalestineIn this study, we synthesized benzodioxol carboxamide derivatives and investigated their antidiabetic potential. The synthesized compounds (<b>Ia-Ic</b> and <b>IIa-IId</b>) underwent characterization via HRMS, <sup>1</sup>H-, <sup>13</sup>CAPT-NMR, and MicroED. Their efficacy against α-amylase was assessed in vitro, while MTS assays were employed to gauge cytotoxicity across cancer and normal cell lines. Additionally, the antidiabetic impact of compound <b>IIc</b> was evaluated in vivo using a streptozotocin-induced diabetic mice model. Notably, <b>IIa</b> and <b>IIc</b> displayed potent α-amylase inhibition (IC<sub>50</sub> values of 0.85 and 0.68 µM, respectively) while exhibiting a negligible effect on the Hek293t normal cell line (IC<sub>50</sub> > 150 µM), suggesting their safety. Compound <b>IId</b> demonstrated significant activity against four cancer cell lines (26–65 µM). In vivo experiments revealed that five doses of <b>IIc</b> substantially reduced mice blood glucose levels from 252.2 mg/dL to 173.8 mg/dL in contrast to the control group. The compelling in vitro anticancer efficacy of <b>IIc</b> and its safety for normal cells underscores the need for further in vivo assessment of this promising compound. This research highlights the potential of benzodioxol derivatives as candidates for the future development of synthetic antidiabetic drugs.https://www.mdpi.com/2218-273X/13/10/1486benzodioxolα-amylasecytotoxicitymicemicroEDstreptozotocin |
| spellingShingle | Mohammed Hawash Derar Al-Smadi Anil Kumar Barbara Olech Paulina Maria Dominiak Nidal Jaradat Sarah Antari Sarah Mohammed Ala’a Nasasrh Murad Abualhasan Ahmed Musa Shorooq Suboh İrfan Çapan Mohammad Qneibi Hiba Natsheh Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal Model Biomolecules benzodioxol α-amylase cytotoxicity mice microED streptozotocin |
| title | Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal Model |
| title_full | Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal Model |
| title_fullStr | Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal Model |
| title_full_unstemmed | Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal Model |
| title_short | Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal Model |
| title_sort | characterization and investigation of novel benzodioxol derivatives as antidiabetic agents an in vitro and in vivo study in an animal model |
| topic | benzodioxol α-amylase cytotoxicity mice microED streptozotocin |
| url | https://www.mdpi.com/2218-273X/13/10/1486 |
| work_keys_str_mv | AT mohammedhawash characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT deraralsmadi characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT anilkumar characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT barbaraolech characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT paulinamariadominiak characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT nidaljaradat characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT sarahantari characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT sarahmohammed characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT alaanasasrh characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT muradabualhasan characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT ahmedmusa characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT shorooqsuboh characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT irfancapan characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT mohammadqneibi characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel AT hibanatsheh characterizationandinvestigationofnovelbenzodioxolderivativesasantidiabeticagentsaninvitroandinvivostudyinananimalmodel |