Synthesis and study of benzofuran-pyran analogs as BMP-2 targeted osteogenic agents

Kushwaha, Pragati; Tripathi, Ashish Kumar; Gupta, Sandeep; Kothari, Priyanka; Upadhyay, Akanksha; Ahmad, Naseer; Sharma, Tanuj; Siddiqi, Mohd Imran; Trivedi, Ritu; Sashidhara, Koneni V.

doi:10.1016/j.ejmech.2018.06.062

Cited by 23 publications

(13 citation statements)

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“…Pyrans were also extensively studied for their osteogenic activities [28,29]. Observations by us confirm that compound 4e is known for its osteogenic [30] and anti lipotoxic [31] effects. This led us to explore the potential of Benzofuran-dihydropyridine hybrids in glucocorticoid induced osteoporosis.…”

Section: Introductionmentioning

confidence: 66%

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Benzofuran pyran hybrid prevents glucocorticoid induced osteoporosis in mice via modulation of canonical Wnt/β-catenin signaling

et al. 2022

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Glucocorticoid induced osteoporosis (GIOP) is the second most leading cause of osteoporosis. We have identified a compound, a benzofuran pyran hybrid compound 4e that has osteogenic potential and we wanted to assess its efficacy in GIOP in male mice. We assessed the effect of dexamethasone and compound 4e on primary osteoblasts using various cell based and immunofluorescence assays. For in vivo studies we administered methylprednisolone and compound 4e as a prophylactic measure in male Balb/c mice for 28 days and then evaluated the effect on bone microarchitecture by microCT, bone formation by histology along with clinically relevant bone markers. Compound 4e preserved osteoblast differentiation as evident by higher ALP positive cells and mineralization in compound treated groups. Compound 4e also increased the expression of osteogenic genes. This compound guarded β-catenin expression both in vitro and in vivo as confirmed by western blot and immunofluorescence assays. This led to the preservation of bone microarchitecture and cortical thickness at 2.5 mg kg −1 and 5 mg kg −1 doses. Further compound 4e enhanced bone formation rate and regulated osteocyte death. The osteogenic potential of compound 4e was reflected by an increased level of serum marker osteocalcin and decreased levels of SOST and CTX-I. Overall, Compound 4e is able to overcome the catabolic effect of dexamethasone on bone by targeting the canonical WNT/β-catenin signaling as evidenced by both in vitro and in vivo studies.

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Section: Introductionmentioning

confidence: 66%

“…Many natural benzofurans have physiological, pharmacological, and toxic effects [ 61 ]. Compound 4e is already known for its osteogenic activity [ 30 ]. Excess glucocorticoid is associated with increased bone marrow fat [ 41 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Benzofuran pyran hybrid prevents glucocorticoid induced osteoporosis in mice via modulation of canonical Wnt/β-catenin signaling

et al. 2022

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“…1 An imbalance in the homeostasis of bone remodeling that causes greater bone resorption over bone formation results in osteoporosis, which is characterized by low bone mass and structurally compromised bone tissue, thereby predisposing bones to a high risk of fractures. 2 Osteoporosis is not only associated with compromised bone mechanical strength but also a decreased quality of life. According to recent studies, osteoporosis afflicts about 200 million globally and this number is expected to surge 2-fold by 2040.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Galloyl Conjugates of Flavanones as BMP-2 Upregulators with Promising Bone Anabolic and Fracture Healing Properties

et al. 2021

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The molecular hybridization concept led us to design a series of galloyl conjugates of flavanones that have potent osteoblast differentiation ability in vitro and promote bone formation in vivo. An array of in vitro studies, especially gene expression of osteogenic markers, evinced compound 5e as the most potent bone anabolic agent, found to be active at 1 pM, which was then further assessed for its osteogenic potential in vivo. From in vivo studies on rat calvaria and a fracture defect model, we inferred that compound 5e, at an oral dose of 5 mg/(kg day), increased the expression of osteogenic genes (RUNX2, BMP-2, Col1, and OCN) and the bone formation rate and significantly promoted bone regeneration at the fracture site, as evidenced by the increased bone volume/tissue fraction compared with vehicle-treated rats. Furthermore, structure–activity relationship studies and pharmacokinetic studies suggest 5e as a potential bone anabolic lead for future osteoporosis drug development.

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“…According to a literature survey, xanthene derivatives are endowed with various biological activities, including potent antimicrobial [ 21 ], analgesic [ 22 ], antimalarial [ 23 ], anti-inflammatory [ 24 ], antiviral [ 25 ], antioxidant [ 26 ], antiproliferative activity [ 27 ], anticancer [ 28 ], and urease activity [ 29 ]; inhibition of trypanothione reductase [ 23 ]; bone morphogenetic protein (BMP-2)-targeted osteogenic agents [ 30 ]; selective positive allosteric modulators of the δ-opioid receptors [ 31 ]; and estrogen receptors [ 32 ]. The structures of biologically active xanthene analogues are presented in Figure 1 .…”

Section: Introductionmentioning

confidence: 99%

ChCl: Gly (DESs) Promote Environmentally Benign Synthesis of Xanthene Derivatives and Their Antitubercular Activity

et al. 2021

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A ChCl: Gly (DESs) promoted environmentally benign method was developed for the first time using the reaction of aryl aldehydes and dimedone to give excellent yields of xanthene analogues. The major application of this present protocol is the use of green solvent, a wide range of substrate, short reaction times, ease of recovery, the recyclability of the catalyst, high reaction yield, and ChCl: Gly as an alternative catalyst and solvent. In addition to this, all the synthesized compounds were evaluated for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 3d, 3e, 3f, and 3j showed significant antitubercular activity against MTB and M. bovis strains with minimum inhibitory concentration (MIC) values of 2.5−15.10 µg/mL and 0.26–14.92 µg/mL, respectively. The compounds 3e, 3f, and 3j were found to be nontoxic against MCF-7, A549, HCT 116, and THP-1 cell lines. All the prepared compounds were confirmed by 1H NMR and 13C NMR analysis.

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Synthesis and study of benzofuran-pyran analogs as BMP-2 targeted osteogenic agents

Cited by 23 publications

References 44 publications

Benzofuran pyran hybrid prevents glucocorticoid induced osteoporosis in mice via modulation of canonical Wnt/β-catenin signaling

Benzofuran pyran hybrid prevents glucocorticoid induced osteoporosis in mice via modulation of canonical Wnt/β-catenin signaling

Synthesis and Evaluation of Galloyl Conjugates of Flavanones as BMP-2 Upregulators with Promising Bone Anabolic and Fracture Healing Properties

ChCl: Gly (DESs) Promote Environmentally Benign Synthesis of Xanthene Derivatives and Their Antitubercular Activity

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