Experimental validation and docking studies of flavone derivatives on aldose reductase involved in diabetic retinopathy, neuropathy, and nephropathy

Sekhar, P. Nataraj; Kishor, P. B. Kavi; Zubaidha, P. K.; Hashmi, A. M.; Kadam, Tukaram; Anandareddy, Lakkireddy; Maeyer, Marc De; Kumar, K. Naveen; Bhaskar, Baki Vijaya; Munichandrababu, Tirumalasetty; Ganugapati, Jayasree; Narayana, P. V. B. S.; Gyananath, G.

doi:10.1007/s00044-010-9412-4

Cited by 7 publications

(3 citation statements)

References 44 publications

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“…Additionally, there was an upregulation of inflammatory genes including Mtor, Tgfb1, and tnf. These findings align with our earlier hypotheses and support the proposed pathway involving the role of adiponectin [98][99][100] Future Directions and Challenges: A multimodal strategy is required for future developments in adiponectin-based diabetic therapy. Adiponectin receptor agonists are being developed by researchers in order to imitate the positive effects of adiponectin on insulin sensitivity and glucose metabolism.…”

Section: Single Cell Data From Db/db Mice Pancreatic Islet Cellssupporting

confidence: 89%

<strong>Adiponectin: A Promising Target for the Treatment of Diabetes and Its Complications </strong>

Begum,

Choubey,

Tirumalasetty

et al. 2023

Preprint

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Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, presents a formidable global health challenge with its associated complications. Adiponectin, an adipocyte-derived hormone, has emerged as a significant player in glucose metabolism and insulin sensitivity. Beyond its metabolic effects, adiponectin exerts anti-inflammatory, anti-oxidative, and vasoprotective properties, making it an appealing therapeutic target for mitigating diabetic complications. The molecular mechanisms by which adiponectin impacts critical pathways implicated in diabetic nephropathy, retinopathy, neuropathy, and cardiovascular problems are thoroughly examined in this study. In addition, we explore possible treatment options for increasing adiponectin levels or improving its downstream signaling. The multifaceted protective roles of adiponectin in diabetic complications suggest its potential as a novel therapeutic avenue. However, further translational studies and clinical trials are warranted to fully harness the therapeutic potential of adiponectin in the management of diabetic complications. This review highlights adiponectin as a promising target for the treatment of diverse diabetic complications and encourages continued research in this pivotal area of diabetes therapeutics.

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Section: Single Cell Data From Db/db Mice Pancreatic Islet Cellssupporting

confidence: 89%

<strong>Adiponectin: A Promising Target for the Treatment of Diabetes and Its Complications </strong>

Begum,

Choubey,

Tirumalasetty

et al. 2023

Preprint

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“…One such important repair enzyme is poly (ADP-ribose) polymerase 1 (PARP1) [4] [5]. Several PARP1 inhibitors like nicotinamide, benzamide, 3-amino benzamide (3AB), 9-phenylacridine (ACPH), NU1025, NU1088, PD128763 are often used in conjunction with cisplatin to make it effective at low doses [5]. Several avones are also known to have PARP1 inhibitory activities [6], among them a synthetic avone derivative is 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO).…”

Section: Introductionmentioning

confidence: 99%

“…From our earlier work based on in silico studies, we have observed that 4NCO could bind at the catalytic site of PARP1 thereby acting as a potent competitive inhibitor hindering the entry of nicotinamide adenine dinucleotide (NAD + ), the natural substrate of PARP1 [7]. 4NCO is a biologically potent avone derivative that also possesses anti-in ammatory, anxiolytic, antioxidant, antitumor and anti-metastatic activities and also known for its tyrosine kinase, BDZ receptor, CDK2, CK2, aldose reductase and DNA binding properties [8] [9][10] [11] [12]. In this work, we have therefore investigated the possible synergism between 4NCO and cisplatin in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

A375 melanoma cells are sensitized to cisplatin-induced toxicity by a synthetic nitro-flavone derivative 2-(4-Nitrophenyl)-4H-chromen-4-one through inhibition of PARP1

Mitra

Ghosh

2021

Mol Biol Rep

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Background: Cisplatin has been extensively used in therapeutics for its broad-spectrum anticancer activity and frequently used for the treatment of solid tumors. However, it presents several side-effects and several cancers develop resistance. Combination therapy of cisplatin with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors has been effective in increasing its e cacy at lower doses.Methods and Results: In this work, we have shown that the nitro-avone derivative, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), can improve the sensitivity of cancer cells to cisplatin through inhibition of PARP1. The effect of 4NCO on cisplatin toxicity was studied through combination therapy in both exponential and density inhibited A375 melanoma cells. Combination index (CI) was determined from isobologram analysis. The mechanism of cell killing was assessed by lactate dehydrogenase (LDH) assay. Temporal nicotinamide adenine dinucleotide (NAD + ) assay was done to show the inhibition of PARP1. We also performed in silico molecular modeling studies to know the binding mode of 4NCO to a modeled PARP1-DNA complex containing cisplatin-crosslinked adduct. The results from both in silico and in cellulo studies con rmed that PARP1 inhibition by 4NCO was most effective in sensitizing A375 melanoma cells to cisplatin. Isobologram analysis revealed that 4NCO reduced cell viability both in exponential and density inhibited A375 cells synergistically. The combination led to cell death through apoptosis. Conclusion:The synthetic nitro-avone derivative 4NCO effectively inhibited the important nuclear DNA repair enzyme PARP1 and therefore, could complement the DNA-damaging anticancer drug cisplatin in A375 cells and thus, could act as a potential adjuvant to cisplatin in melanoma therapy.

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Challenges in docking 2′-hydroxy and 2′,4′-dihydroxychalcones into the binding site of ALR2

et al. 2012

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Experimental validation and docking studies of flavone derivatives on aldose reductase involved in diabetic retinopathy, neuropathy, and nephropathy

Cited by 7 publications

References 44 publications

<strong>Adiponectin: A Promising Target for the Treatment of Diabetes and Its Complications </strong>

<strong>Adiponectin: A Promising Target for the Treatment of Diabetes and Its Complications </strong>

A375 melanoma cells are sensitized to cisplatin-induced toxicity by a synthetic nitro-flavone derivative 2-(4-Nitrophenyl)-4H-chromen-4-one through inhibition of PARP1

Challenges in docking 2′-hydroxy and 2′,4′-dihydroxychalcones into the binding site of ALR2

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