Design, synthesis, and biological evaluation of some novel indolizine derivatives as dual cyclooxygenase and lipoxygenase inhibitor for anti-inflammatory activity

Shrivastava, Sushant K.; Srivastava, Pavan; Bandresh, Robin; Tripathi, Prem Prakash; Tripathi, Avanish

doi:10.1016/j.bmc.2017.06.027

Cited by 49 publications

(29 citation statements)

References 32 publications

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“…This is by far the first reported study on HRBC membrane stabilization study on BG. The GC-MS analysis of methanolic extract reported several phytoconstituents with anti-inflammatory activity such as Indolizine [37], 9,12,15-Octadecatrienoic acid [38], Phytol [39], Squalene [40]. The presence of such compounds could be the reason for the activity of extracts.…”

Section: Discussionmentioning

confidence: 99%

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Bioactivity evaluations of leaf extract fractions from young barley grass and correlation with their phytochemical profiles

Panthi

Subba

Raut

et al. 2020

BMC Complement Med Ther

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Background: The pressed juice of Barley Grass (BG) has become very popular among people for various assumed benefits along with many testimonies of people who have been healed from various ailments such as anemia, cancer, GI problems by consuming BG. The aim of our research was to validate the claims of its medicinal values such as chemo-protective action, high anti-oxidants, RBC membrane stabilization activity, and toxicity level. Methods: Extracts of hexane, ethyl acetate and methanol were quantitatively estimated for total phenolic contents (TPC) and total flavonoid contents (TFC). The same extracts were assessed for their antioxidative potentials with the use of DPPH free radical scavenging assay followed by determination of HRBC membrane stabilization method, Brine Shrimp Lethality Assay (BSLA) and GC-MS analysis. Results: All the extracts showed high TPC and TFC along with the stronger correlation with the antioxidant activity of the extracts suggesting phenolics and flavonoids contents of the extract might be attributed to showing antioxidant activity. The methanolic and ethyl acetate extracts of the plant also showed remarkable antiinflammatory activity where methanolic extracts had the lowest EC50. During Brine Shrimp Lethality Assay, all extracts of BG were found to be bioactive and the degree of lethality was found to be concentration dependent. The GC-MS analysis of the methanolic extract of BG revealed 23 compounds which are reported to possess different biological activities. Conclusion: The study reveals the strong antioxidant and RBC membrane stabilization activity of BG. The Brine Shrimp Lethality Assay found extracts to be bioactive suggesting extracts as a promising candidate for plantderived anti-tumor compounds. Further, studies are needed to validate the data on cancer cell lines.

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Section: Discussionmentioning

confidence: 99%

“…These compounds are reported to possess different activities. For ex, Indolizine has anti-inflammatory properties [37]. Phytol is a diterpene which is reported to have anti-inflammatory and cancer preventive properties [39].…”

Section: Discussionmentioning

confidence: 99%

Bioactivity evaluations of leaf extract fractions from young barley grass and correlation with their phytochemical profiles

Panthi

Subba

Raut

et al. 2020

BMC Complement Med Ther

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“…A molecular docking study was performed using Gold score 5.1 software to predict and compare the selectivity of coumarin-pyrazoline derivatives against COX-2 (PDB 3LN1), 56,57 COX-1 (PDB 3KK6) 56,58 and 5-LOX (PDB 3V99) enzymes. 56,59 The affinities of the synthesized compounds were evaluated in terms of Gold score and it was observed that the synthesized compounds 7a-g showed good binding interaction with the active site of the COX-2 enzyme as compared to COX-1 and 5 LOX, which were also taken into consideration to evaluate the selectivity (Table S4 †). Further, molecular docking results revealed that the most potent compound 7a was fitted well to the active site of COX-2 with Gold score = 88.25, as compared to celecoxib (Gold score = 96.42; Table S4 †).…”

Section: 24mentioning

confidence: 99%

Rationally synthesized coumarin based pyrazolines ameliorate carrageenan induced inflammation through COX-2/pro-inflammatory cytokine inhibition

et al. 2019

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“…They are found in a large number of natural products such as (±)-homocrepidine A (Hu et al, 2015), tashiromine (Marsden and McElhinney, 2008), swainsonine (Lee et al, 2013), Pandalisines A and B (Cheng et al, 2015), Flueggedine (Zhao et al, 2013), and so on. Recent studies have indicated that indolizines exhibit a broad range of biological activities including anti-herpesvirus (De Bolle et al, 2004), cyclooxygenase and lipoxygenase inhibition (Shrivastava et al, 2017), inhibition of Mycobacterium tuberculosis (Gundersen et al, 2007), and Ach receptor agonist (Xue et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

A Novel Indolizine Derivative Induces Apoptosis Through the Mitochondria p53 Pathway in HepG2 Cells

et al. 2019

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Indolizine derivatives are a class of compounds with excellent biological activity. In this study, a series of indolizine derivatives, compound 1 (C1), compound 2 (C2), compound 3 (C3), and compound 4 (C4), were synthesized. 3-(4,5-dimethylthiazole)-2,5-diphenyltetraazolium bromide (MTT) assay was used to evaluate their cytotoxicity against HepG2 (p53-wild), A549, and HeLa cell lines. HepG2 cells apoptosis induced by C3 was determined using Hoechst staining and acridine orange/ethidium bromide staining. Cells’ apoptotic ratio was measured by Annexin V–FITC/PI double staining. Changes in mitochondrial membrane potential and intracellular reactive oxygen species (ROS) in HepG2 cells after C3 treatment were determined. Immunofluorescence staining and Western blot analysis were carried out to detect p53 levels and analyze the apoptosis-associated proteins, respectively. Moreover, the cytotoxic activity of C3 was examined in two other hepatocellular carcinoma (HCC) cell lines with different p53 status including Huh-7 cells (p53-mutant) and Hep3B cells (p53-null). The results indicated that C3 showed stronger inhibition towards HepG2 cells than other cell lines. Fluorescent staining and flow cytometry analysis confirmed that C3 induced apoptosis of HepG2 cells. C3 could also increase intracellular ROS and cause a decrease in the mitochondrial membrane potential. C3 promoted p53 activation and increased p53 accumulation in nuclei. The expression of p53 and Bax was increased with the down-regulation of Bcl-2, which promoted the release of cytochrome c and caspase-3 activation. Collectively, the study demonstrated that C3 caused HepG2 cell apoptosis via the mitochondria p53 pathway. These results inspired us to further develop indolizine derivatives as potential potent inhibitors against liver cancer.

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Design, synthesis, and biological evaluation of some novel indolizine derivatives as dual cyclooxygenase and lipoxygenase inhibitor for anti-inflammatory activity

Cited by 49 publications

References 32 publications

Bioactivity evaluations of leaf extract fractions from young barley grass and correlation with their phytochemical profiles

Bioactivity evaluations of leaf extract fractions from young barley grass and correlation with their phytochemical profiles

Rationally synthesized coumarin based pyrazolines ameliorate carrageenan induced inflammation through COX-2/pro-inflammatory cytokine inhibition

A Novel Indolizine Derivative Induces Apoptosis Through the Mitochondria p53 Pathway in HepG2 Cells

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