Catalytic Access to Succinimide Products Containing Stereogenic Quaternary Carbons

Sadiq, Abdul; Nugent, Thomas C.

doi:10.1002/slct.202003664

Cited by 25 publications

(27 citation statements)

References 31 publications

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“…Similarly, the succinimide is a known class of drugs for neuropharmacology and inflammation [ 44 ]. Various derivatives of succinimide-type compounds can be synthesized with different methods [ 51 – 54 ]. In our research, we noticed that compounds 2 , 4, and 5 are potent antioxidant molecules.…”

Section: Resultsmentioning

confidence: 99%

Antioxidant Molecules Isolated from Edible Prostrate Knotweed: Rational Derivatization to Produce More Potent Molecules

Mahnashi

Alyami

Alqahtani

et al. 2022

Oxidative Medicine and Cellular Longevity

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Prostrate knotweed also called Polygonum aviculare is an important edible plant. The polygonum is majorly known for the phenolics and antioxidants. The antioxidants combat the excessive free radicals within the body. The excessive free radicals are implicated in various other diseases like diabetes, Alzheimer’s, and inflammation. This study was aimed at exploring the antioxidant bioactives and their derivatizations to produce new molecules with advanced pharmacological features. We have isolated six compounds (1–6) from Polygonum aviculare. Furthermore, rational-based chemical derivatives for compound 5 have been formed for the management of diabetes, Alzheimer’s, and inflammation. In preliminary antioxidant studies, all the isolated compounds (1–6) showed potential results against DPPH and ABTS free radicals. Based on the IC50 and chemical nature of the compounds, compound 5 was subjected to derivatization. Keeping the phenolic part of compound 5 unaffected, hydroxy succinimide (5A) and thiazolidinedione (5B) were synthesized. The compound 5A was found to be a potent inhibitor of AChE, BChE, COX-1, COX-2, 5-LOX, and DPPH giving IC50 values of 10.60, 15.10, 13.91, 1.08, 0.71, and 1.05 μM, respectively. The COX-2 selectivity of compound 5A was found at 12.9. The compound 5B was found to be a potent multitarget antidiabetic agent giving IC50 values of 15.34, 21.83, 53.28, and 1.94 μM against α-glucosidase, α-amylase, protein tyrosine phosphatase 1B, and DPPH. Docking studies were performed to manipulate the binding interactions. The docking pose of all the tested compounds was found to have increased binding affinity against all tested targets that supported the in vitro results. Our results showed that Polygonum aviculare is a rich source of antioxidant compounds. The two new derivatives have enhanced pharmacological features to treat diabetes, inflammation, and Alzheimer’s disease.

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Section: Resultsmentioning

confidence: 99%

Antioxidant Molecules Isolated from Edible Prostrate Knotweed: Rational Derivatization to Produce More Potent Molecules

Mahnashi

Alyami

Alqahtani

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…The basic structure of all succinimides contain a cyclic five membered ring with two amide carbonyls connected by an amide nitrogen for both. 2 , 12 , 21 Various researchers have substituted the basic nucleus of succinimide and have formed a diverse array of substituted derivatives of it. 46 Being a vital class of medicinally important compounds, succinimide have shown various pharmacological potentials.…”

Section: Resultsmentioning

confidence: 99%

“…The combined organic layer was dried and was purified by column chromatography using n-hexane and an ethyl acetate solvent system. 12 …”

Section: Methodsmentioning

confidence: 99%

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Synthesis of Michael Adducts as Key Building Blocks for Potential Analgesic Drugs: In vitro, in vivo and in silico Explorations

Ahmad¹,

Mahnashi²,

Alyami³

et al. 2021

DDDT

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Background Organocatalytic asymmetric Michael addition is a strong approach for C-C bond formation. The objective of the study is to design molecules by exploiting the efficiency of Michael Adducts. We proceeded with the synthesis of Michael adducts by tailoring the substitution pattern on maleimide and trans-β-nitro styrene as Michael acceptors. The synthesized compounds were evaluated for dual cyclooxygenases (COX) and lipoxygenase (LOX) inhibition. Methods The compounds (4, 9–11) were synthesized through Michael additions. The cyclooxygenases (COX-1 and 2) and lipoxygenase (5-LOX) assays were used for in vitro evaluations of compounds. After the acute toxicity studies, the in vivo analgesic potential was determined with acetic acid induced writhing, tail immersion, and formalin tests. Furthermore, the possible roles of adrenergic and dopaminergic receptors were also studied. Extensive computational studies were performed to get a better understanding regarding the binding of this compound with protein target. Results Four Michael adducts (4, 9–11) were synthesized. Compound 4 was obtained in enantio- and diastereopure form. The stereopure compound 4 showed encouraging COX-1 and-2 inhibitions with IC 50 values of 128 and 65 μM with SI of 1.94. Benzyl derivative 11 showed excellent COX-2 inhibition with the IC 50 value of 5.79 μM and SI value 7.96. Compounds 4 and 11 showed good results in in vivo models of analgesia like acetic acid test, tail immersion, and formalin tests. Our compounds were not active in dopaminergic and adrenergic pathways and so were acting centrally. Through extensive computational studies, we computed binding energies, and pharmacokinetic predictions. Conclusion Our findings conclude that our synthesized Michael products (pyrrolidinedione 4 and nitroalkane 11) can be potent centrally acting analgesics. Our in silico predictions suggested that the compounds have excellent pharmacokinetic properties. It is concluded here that dual inhibition of COX/LOX pathways provides a convincing step towards the discovery of safe lead analgesic molecules.

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“…TZD is antidiabetic; therefore, it is presumed that ketones derivatives of succinimides have antidiabetic potential on the basis of its structure resemblance to that of TZDs. There is no literature on the antidiabetic potential of ketone derivatives of succinimides [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antioxidant, and Antidiabetic Activities of Ketone Derivatives of Succinimide

Waheed

Shah

Hussain

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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The prevalence of diabetes mellitus is persistently increasing globally creating a serious public health affliction. Diabetes mellitus is categorized into two major types designated as type I and Type II. Type I diabetes mellitus is characterized by complete lack of secretion of insulin, while Type II diabetes mellitus is the resistance of peripheral tissues to the action of insulin and inadequate compensatory secretion of insulin. Chronic hyperglycemia associated with diabetes causes failure of cardiovascular system, nervous system, kidneys, and eyes. At present, different types of drugs are used for the management of diabetes, but each of them is associated with more or less serious side effects. Therefore, we need to develop new therapeutic agents that have better efficacy and safety profile. In this study, three ketone derivatives of succinimides were synthesized based on Michael addition and characterized using NMR. All the synthesized compounds were checked for their in vitro α-amylase and α-glucosidase inhibitory activities. Further the synthesized compounds were also explored for their antioxidant activities, i.e, DPPH and ABTS assays. Based on the in vitro results, the synthesized compounds were further evaluated for in vivo antidiabetic activity. The synthesized compounds were (2-oxocyclohexyl)-1-phenylpyrrolidine-2,5-dione (BW1), benzyl-3-(2-oxocyclohexyl) pyrrolidine-2,5-dione (BW2), and (4-bromophenyl)-3-(2-oxocyclohexyl) pyrrolidine-2,5-dione (BW3). BW1 showed the highest inhibitory activity for DPPH causing 83.03 ± 0.48 at 500 μg/ml with IC50 value of 10.84 μg/ml and highest inhibitory activity for ABTS causing 78.35 ± 0.23 at 500 μg/ml with IC50 value of 9.40 μg/ml against ascorbic acid used as standard. BW1 also exhibited the highest activity against α-amylase and α-glucosidase inhibition causing 81.60 ± 0.00 at concentrations of 500 μg/ml with IC50 value of 13.90 μg/ml and 89.08 ± 1.04 at concentrations of 500 μg/ml with IC50 value of 10.49 μg/ml, respectively, against the standard drug acarbose.

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Catalytic Access to Succinimide Products Containing Stereogenic Quaternary Carbons

Cited by 25 publications

References 31 publications

Antioxidant Molecules Isolated from Edible Prostrate Knotweed: Rational Derivatization to Produce More Potent Molecules

Antioxidant Molecules Isolated from Edible Prostrate Knotweed: Rational Derivatization to Produce More Potent Molecules

Synthesis of Michael Adducts as Key Building Blocks for Potential Analgesic Drugs: In vitro, in vivo and in silico Explorations

Synthesis, Antioxidant, and Antidiabetic Activities of Ketone Derivatives of Succinimide

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