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3 results on '"Derar Al-Smadi"'

1. Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal Model

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, and Hiba Natsheh

Subjects
benzodioxol, α-amylase, cytotoxicity, mice, microED, streptozotocin, Microbiology, QR1-502
Abstract

In this study, we synthesized benzodioxol carboxamide derivatives and investigated their antidiabetic potential. The synthesized compounds (Ia-Ic and IIa-IId) underwent characterization via HRMS, 1H-, 13CAPT-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 IIc was evaluated in vivo using a streptozotocin-induced diabetic mice model. Notably, IIa and IIc displayed potent α-amylase inhibition (IC50 values of 0.85 and 0.68 µM, respectively) while exhibiting a negligible effect on the Hek293t normal cell line (IC50 > 150 µM), suggesting their safety. Compound IId demonstrated significant activity against four cancer cell lines (26–65 µM). In vivo experiments revealed that five doses of IIc 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 IIc 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.

Published
2023
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2. New Stereoselective Biocatalysts for Carboligation and Retro-Aldol Cleavage Reactions Derived from <scp>d</scp>-Fructose 6-Phosphate Aldolase

Author

Thilak Reddy Enugala, Mikael Widersten, Derar Al-Smadi, Sarah Engel, Candice Gautier, and Huan Ma

Subjects
Phenylacetaldehyde, biology, 010405 organic chemistry, Stereochemistry, Escherichia coli Proteins, Hydroxyacetone, Aldolase A, Fructosephosphates, Enantioselective synthesis, Substrate (chemistry), 010402 general chemistry, 01 natural sciences, Biochemistry, Substrate Specificity, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Aldol reaction, Fructose-Bisphosphate Aldolase, Escherichia coli, biology.protein, Stereoselectivity, Saturated mutagenesis
Abstract

d-Fructose 6-phosphate aldolase (FSA) catalyzes the asymmetric cross-aldol addition of phenylacetaldehyde and hydroxyacetone. We conducted structure-guided saturation mutagenesis of noncatalytic active-site residues to produce new FSA variants, with the goal of widening the substrate scope of the wild-type enzyme toward a range of para- and meta-substituted arylated aldehydes. After a single generation of mutagenesis and selection, enzymes with diverse substrate selectivity scopes were identified. The kinetic parameters and stereoselectivities for a subset of enzyme/substrate combinations were determined for the reactions in both the aldol addition and cleavage reaction directions. The achieved collection of new aldolase enzymes provides new tools for controlled asymmetric synthesis of substituted aldols.

Published
2018

3. Synthesis of Substrates for Aldolase-Catalysed Reactions: A Comparison of Methods for the Synthesis of Substituted Phenylacetaldehydes

Author

Jan Kihlberg, Thomas Norberg, Thilak Reddy Enugala, Derar Al-Smadi, and Mikael Widersten

Subjects
biology, 010405 organic chemistry, Organic Chemistry, Aldolase A, chemistry.chemical_element, Manganese, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Benzaldehyde, chemistry.chemical_compound, chemistry, Yield (chemistry), Homologation reaction, biology.protein, Swern oxidation, Organic chemistry
Abstract

Methods for the synthesis of phenylacetaldehydes (oxidation, one-carbon chain extension) were compared by using the synthesis of 4-methoxyphenylacetaldehyde as a model example. Oxidations of 4-methoxyphenylethanol with activated DMSO (Swern oxidation) or manganese dioxide gave unsatisfactory results; whereas oxidation with 2-iodoxybenzoic acid (IBX) produced 4-methoxyphenylacetaldehyde in reasonable (75%) yield. However, Wittig-type one-carbon chain extension with methoxymethylene-triphenylphosphine followed by hydro­lysis gave an excellent (81% overall) yield of 4-methoxyphenylacetaldehyde from 4-methoxybenzaldehyde (a cheap starting material). This approach was subsequently used to synthesise a set of 10 substituted phenylacetaldehydes in good to excellent yields.

Published
2018

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