3-(((1S,3S)-3-((R)-Hydroxy(4-(trifluoromethyl)phenyl)methyl)-4-oxocyclohexyl)methyl)pentane-2,4-dione: Design and Synthesis of New Stereopure Multi-Target Antidiabetic Agent

Sadiq, Abdul; Mahnashi, Mater H.; Rashid, Umer; Jan, Muhammad; Alshahrani, Mohammed Abdulrahman

doi:10.3390/molecules27103265

Cited by 18 publications

(19 citation statements)

References 53 publications

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“…The in vitro α -amylase inhibition of the tested compounds was evaluated [ 51 ]. However, the enzyme α -amylase is present in pancreatic juice and saliva which can convert larger polysaccharides into smaller particles [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Succinimide Derivatives as Antioxidant Anticholinesterases, Anti-α-Amylase, and Anti-α-Glucosidase: In Vitro and In Silico Approaches

Alshehri

Mahnashi

Sadiq

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Based on the diverse pharmacological potency and the structural features of succinimide, this research considered to synthesize succinimide derivatives. Moreover, these compounds were estimated for their biological potential in terms of anti-diabetic, anti-cholinesterase, and anti-oxidant capacities. The compounds were synthesized through Michael addition of various ketones to N-aryl maleimides. Similarly, the MOE software was used for the molecular docking study to explore the binding mode of the potent compounds against different enzymes. In the anti-cholinesterase activity, the compounds MSJ2 and MSJ10 exhibited outstanding activity against acetylcholinesterase (AChE), i.e., 91.90, 93.20%, and against butyrylcholinesterase (BChE), i.e., 97.30, 91.36% inhibitory potentials, respectively. The compounds MSJ9 and MSJ10 exhibited prominent α-glucosidase inhibitory potentials, i.e., 87.63 and 89.37 with IC50 value of 32 and 28.04 μM, respectively. Moreover, the compounds MSJ2 and MSJ10 revealed significant scavenging activity against DPPH free radicals with IC50 values of 2.59 and 2.52, while against ABTS displayed excellent scavenging potential with IC50 values 7.32 and 3.29 μM, respectively. The tentative results are added with molecular docking studies in the active sites of enzymes to predict the theoretical protein-ligand binding modes. Further detailed mechanism-based studies in animal models are essential for the in vivo evaluation of the potent compound.

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Section: Discussionmentioning

confidence: 99%

Succinimide Derivatives as Antioxidant Anticholinesterases, Anti-α-Amylase, and Anti-α-Glucosidase: In Vitro and In Silico Approaches

Alshehri

Mahnashi

Sadiq

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…The α-glucosidase and α-amylase assays are very common and well-known tests for determining the preliminary antidiabetic activity of an unknown compound [ 53 ]. The in-vitro antidiabetic potentials of the samples were determined using α-glucosidase and α-amylase assays.…”

Section: Discussionmentioning

confidence: 99%

Phytochemistry, anti-diabetic and antioxidant potentials of Allium consanguineum Kunth

Mahnashi

Alqahtani

Alqarni

et al. 2022

BMC Complement Med Ther

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Aim The study was planned to investigate the phytochemicals, antidiabetic and antioxidant studies of A. consanguineum. Methods The preliminary studies were performed on crude extract and different solvent fractions. Based on the potency, the chloroform fraction was semi-purified to phyto-fractions CHF-1 – 5. Furthermore, CHF-3 was subjected to isolation of pure compounds using column chromatography. The α-glucosidase, α-amylase and antioxidant assays (DPPH, ABTS, H2O2) were performed on all samples. The in-vivo experiments on compounds 1 and 2 were also performed using oral glucose tolerance test. Docking studies were performed on α-glucosidase and α-amylase targets. Results Among all fractions, the chloroform fraction exhibited excellent activities profile giving IC50 values of 824, 55, 117, 58 and 85 μg/ml against α-glucosidase, α-amylase, DPPH, ABTS and H2O2 targets respectively. Among the five semi-purified chloroform phyto-fractions (CHF-1-5), CHF-3 was the leading fraction in activities giving IC50 values of 85.54, 61.19 and 26.58 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Based on the overall potency and physical amount of CHF-3, it was subjected to purification to get compounds 1 and 2. The two compounds were also found potent in in-vitro activities. The observed IC50 values for compound 1 were 7.93, 28.01 and 6.19 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Similarly, the compound 2 exhibited IC50 of 14.63, 24.82 and 7.654 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Compounds 1 and 2 were potent in decreasing the blood glucose levels in experimental animals. Compounds 1 and 2 also showed interactions with the respective enzymes with molecular docking. Conclusions We can conclude that A. Consanguineum is a rich source of natural antidiabetic agents. Bioguided isolation of compound 1 and 2 showed potential inhibitions in all tested in-vitro antidiabetic targets. Further, both the compounds were also able to decrease the blood glucose levels in experimental animals.

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“…The α -amylase inhibitory activity was carried out according to the established protocols for F. indica extracts and isolated compounds [ 60 ] The amylase solution was prepared in phosphate buffer. The solutions of the F. indica and isolated compounds (62.50 to 1000 µg/mL) were added to the amylase solution and allowed to react.…”

Section: Methodsmentioning

confidence: 99%

α-Glucosidase, α-Amylase and Antioxidant Evaluations of Isolated Bioactives from Wild Strawberry

et al. 2022

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Diabetes mellitus is a metabolic disorder and is a global challenge to the current medicinal chemists and pharmacologists. This research has been designed to isolate and evaluate antidiabetic bioactives from Fragaria indica. The crude extracts, semi-purified and pure bioactives have been used in all in vitro assays. The in vitro α-glucosidase, α-amylase and DPPH free radical activities have been performed on all plant samples. The initial activities showed that ethyl acetate (Fi.EtAc) was the potent fraction in all the assays. This fraction was initially semi-purified to obtain Fi.EtAc 1–3. Among the semi-purified fractions, Fi.EtAc 2 was dominant, exhibiting potent IC50 values in all the in vitro assays. Based on the potency and availability of materials, Fi.EtAc 2 was subjected to further purification to obtain compounds 1 (2,4-dichloro-6-hydroxy-3,5-dimethoxytoluene) and 2 (2-methyl-6-(4-methylphenyl)-2-hepten-4-one). The two isolated compounds were characterized by mass and NMR analyses. The compounds 1 and 2 showed excellent inhibitions against α-glucosidase (21.45 for 1 and 15.03 for 2 μg/mL), α-amylase (17.65 and 16.56 μg/mL) and DPPH free radicals (7.62 and 14.30 μg/mL). Our study provides baseline research for the antidiabetic bioactives exploration from Fragaria indica. The bioactive compounds can be evaluated in animals-based antidiabetic activity in future.

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3-(((1S,3S)-3-((R)-Hydroxy(4-(trifluoromethyl)phenyl)methyl)-4-oxocyclohexyl)methyl)pentane-2,4-dione: Design and Synthesis of New Stereopure Multi-Target Antidiabetic Agent

Cited by 18 publications

References 53 publications

Succinimide Derivatives as Antioxidant Anticholinesterases, Anti-α-Amylase, and Anti-α-Glucosidase: In Vitro and In Silico Approaches

Succinimide Derivatives as Antioxidant Anticholinesterases, Anti-α-Amylase, and Anti-α-Glucosidase: In Vitro and In Silico Approaches

Phytochemistry, anti-diabetic and antioxidant potentials of Allium consanguineum Kunth

α-Glucosidase, α-Amylase and Antioxidant Evaluations of Isolated Bioactives from Wild Strawberry

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