<b>ItaCORMs</b>: conjugation with a CO-releasing unit greatly enhances the anti-inflammatory activity of itaconates

Krause, B.; Bauer, Britta; Neudörfl, Jörg‐Martin; Wieder, Thomas; Schmalz, Hans‐Günther

doi:10.1039/d1md00163a

Cited by 5 publications

(3 citation statements)

References 49 publications

(36 reference statements)

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“…For example 4H-Pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-has Anti-oxidant, anti-microbial, laxative and anticancer activities [38]. 4-Methyl itaconate has anti-inflammatory and anticancer potential [38,39]. .alpha.-Terpineol are reported for antioxidant, anticancer, anticonvulsant, antiulcer, antihypertensive and anti-nociceptive [40], It additionally restrains growth and triggers cell death in tumor cells via a mechanism that includes the suppression of NF-κB activity [41].…”

Section: Discussionmentioning

confidence: 99%

GC-MS analysis, Elemental and Nutritional Composition and Biological Investigation of Medicinally Valued Fingerhuthia africana Lehm.

Ullah,

Adil,

Filimban

2023

Preprint

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Fingerhuthia africana Lehm belongs to family Poaceae, is an erect perennial grass used traditionally to cure different diseases. The current study was carried out to find the bioactive compounds by GC-MS, elemental analysis through atomic absorption spectrophotometry, proximate analysis by AOAC, genotoxic activity through comet assay, antioxidant activity through DPPH and antidiarrheal activity through castor oil induce diarrhea followed by charcoal meal on mice model. GC-MS chromatogram represents different compounds detected in the crude extract. Major pharmacological bioactive compounds are 4H-Pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-; 4-Methyl itaconate; .alpha.-Terpineol; 1,2,3-Propanetriol, 1-acetate; Benzofuran, 2,3-dihydro-; Caryophyllene oxide; Hinesol; n-Hexadecanoic acid; 9,12-Octadecadienoic acid (Z,Z)-, methyl ester; Hexadecanoic acid and methyl ester. Elemental analysis of stem, leaves and roots of the plant show the presence of (macro and micro) nutrients such as Ca, Mg, K, Na, Cu, Pb, Zn, Mn, Fe, Cd and Co were absent in all parts. Proximate analysis of different parts revealed the presence of moisture contents (8.57%), ash (9.77%), fats contents (5.96%), fibers contents (45.03%), protein (3.62%), carbohydrates (39.71%) and Gross energy (Kcal/100g) (220.10). The ethanolic extract show dose-dependent genoprotective potential (127.38 ± 1.16), (83.28 ± 0.65), and (44.08 ± 1.40) at 50, 75, and 100 mg/100 ml, respectively, as compared to the methanolic extract which show genotoxic activity (85.13 ± 1.23) at high dose. After 90 minutes at a concentration of 300 (g/ml), methanolic extract demonstrated the greatest antioxidant potential (79.5%), followed by aqueous extract (76.5%). The methanolic extract of F. africana demonstrated antidiarrheal efficacy, with the maximum inhibition of charcoal movement (83.78%) occurring at a dosage of 300 mg/kg, followed by doses of 200 and 100 mg/kg, 73.26% and 59.56%, respectively. The current research highlights that the plant contains a substantial quantity of micro and macro nutrients, possesses high nutritional value, and exhibits pharmacological activities. These properties render the plant suitable for developing remedies to treat various therapeutic diseases.

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Section: Discussionmentioning

confidence: 99%

GC-MS analysis, Elemental and Nutritional Composition and Biological Investigation of Medicinally Valued Fingerhuthia africana Lehm.

Ullah,

Adil,

Filimban

2023

Preprint

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“…Interdisciplinary studies have led to the development of a compound (ItaCORMs) that can release itaconate and CO simultaneously and thus shows better anti-inflammatory effects than itaconate or CO in LPS-stimulated BMDMs [ 52 ]. In addition, some scientists started using itaconate as a biomaterial to produce an anti-inflammatory effect.…”

Section: Itaconate and Its Derivativesmentioning

confidence: 99%

The signaling pathways and therapeutic potential of itaconate to alleviate inflammation and oxidative stress in inflammatory diseases

Shi¹,

Zhou²,

Wei³

et al. 2022

Redox Biology

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“…Upon (intracellular) cleavage of the ester bond, the resulting dienol‐Fe(CO) 3 intermediates (such as rac‐ 5 ) are rapidly oxidized to form Fe 3+ ions under liberation of up to three molecules of CO (Scheme 1). Additionally, we could show that conjugation of the ET‐CORM moiety with anti‐inflammatory active compounds such as itaconates or fumarates led to pronounced synergistic biological effects [17e,f] …”

Section: Introductionmentioning

confidence: 99%

Synthesis of Bifunctional Lipoxin‐Derived Enzyme‐Triggered CO‐Releasing Molecules (LipET‐CORMs)

et al. 2023

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In an attempt to develop new anti-inflammatory agents which act by co-release of carbon monoxide (CO) and a specialized pro-resolving mediator, we designed conjugates of a lipoxin A 4 analogue and an acyloxycyclohexadiene-Fe(CO) 3 complex as an esterase-triggered CO-releasing molecule (ET-CORM). After adjustment of the protecting group strategy, two of such compounds were successfully prepared by total synthesis (12 steps; 4-5 % overall yield) starting from deoxy-d-ribose and exploiting a Wittig olefination and an intermolecular Heck reaction as key CÀ C bond-forming steps. A crucial late reduction of an aryl-ketone moiety in the presence of a highly sensitive dienol ester functionality was achieved with BH 3 -SMe 2 in the presence of catalytic amounts of NaBH 4 . Both target compounds were dose-dependently toxic towards cultured human umbilical vein endothelial cells (HUVEC), with LipET-CORM 1-A being slightly more toxic. While induction of heme oxygenase 1 (HO-1) in HUVEC was observed for both compounds, they did not inhibit TNF-α-mediated VCAM-1 expression in these cells. In M2 polarized macrophages HO-1 expression was more pronounced as compared to M1 polarized macrophages. In both types of macrophages HO-1 expression was downregulated by lipopolysaccharide, but only in M2 macrophages HO-1 expression was rescued by LipET-CORM. 15-Lipoxygenase (15-LO) was only expressed in M2 macrophages and was not influenced by LipET-CORM. Collectively our data demonstrate that LipET-CORMs induce HO-1 expression in endothelial cells and M2 polarized macrophages. The role of the intra-cellular released lipoxin A 4 in resolution of inflammation, however, remains to be assessed.

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ItaCORMs: conjugation with a CO-releasing unit greatly enhances the anti-inflammatory activity of itaconates

Abstract: Endogenous itaconate as well as the gasotransmitter CO have recently been described as powerful anti-inflammatory and immunomodulating agents. However, each of the two agents comes along with a major drawback:...

Cited by 5 publications

References 49 publications

GC-MS analysis, Elemental and Nutritional Composition and Biological Investigation of Medicinally Valued Fingerhuthia africana Lehm.

GC-MS analysis, Elemental and Nutritional Composition and Biological Investigation of Medicinally Valued Fingerhuthia africana Lehm.

The signaling pathways and therapeutic potential of itaconate to alleviate inflammation and oxidative stress in inflammatory diseases

Synthesis of Bifunctional Lipoxin‐Derived Enzyme‐Triggered CO‐Releasing Molecules (LipET‐CORMs)

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