Regioselective synthesis of densely functionalized, enantiopure, sugar–pyrazole hybrids as potential scaffolds for drug discovery

Saquib, Mohammad; Husain, Irfan; Kant, Ravi; Meena, Sanjeev; Gauniyal, Harsh M.; Sinha, Sudhir; Maulik, Prakas R.; Shaw, Arun K.

doi:10.1039/c3ra22287j

Cited by 10 publications

(4 citation statements)

References 48 publications

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“…In this milieu, molecular hybridization can be a very useful tool ( Li and Vederas, 2009 ; Wetzel et al, 2011 ). This approach involves combining two or more pharmacophoric units to obtain novel compounds with enhanced therapeutic properties and is finding increasing applications in the fields of drug discovery and medicinal chemistry ( Meunier, 2008 ; Bosquesi et al, 2011 ; Saquib et al, 2013 ; Tukulula et al, 2013 ; Švenda et al, 2015 ) ( Figure 1 ) ( Tietze et al, 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Natural product-inspired synthesis of coumarin–chalcone hybrids as potential anti-breast cancer agents

Alhakamy,

Saquib,

Sanobar

et al. 2023

Front. Pharmacol.

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Twelve novel neo-tanshinlactone–chalcone hybrid molecules were constructed through a versatile methodology involving the Horner–Wadsworth–Emmons (HWE) olefination of 4-formyl-2H-benzo [h]chromen-2-ones and phosphonic acid diethyl esters, as the key step, and evaluated for anticancer activity against a series of four breast cancers and their related cell lines, viz. MCF-7 (ER + ve), MDA-MB-231 (ER-ve), HeLa (cervical cancer), and Ishikawa (endometrial cancer). The title compounds showed excellent to moderate in vitro anti-cancer activity in a range of 6.8–19.2 µM (IC50). Compounds 30 (IC50 = 6.8 µM and MCF-7; IC50 = 8.5 µM and MDA-MB-231) and 31 (IC50 = 14.4 µM and MCF-7; IC50 = 15.7 µM and MDA-MB-231) exhibited the best activity with compound 30 showing more potent activity than the standard drug tamoxifen. Compound 30 demonstrated a strong binding affinity with tumor necrosis factor α (TNF-α) in molecular docking studies. This is significant because TNFα is linked to MCF-7 cancer cell lines, and it enhances luminal breast cancer cell proliferation by upregulating aromatase. Additionally, virtual ADMET studies confirmed that hybrid compounds 30 and 31 met Lipinski’s rule; displayed high bioavailability, excellent oral absorption, favorable albumin interactions, and strong penetration capabilities; and improved blood–brain barrier crossing. Based on the aforementioned results, compound 30 has been identified as a potential anti-breast cancer lead molecule.

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Section: Introductionmentioning

confidence: 99%

Natural product-inspired synthesis of coumarin–chalcone hybrids as potential anti-breast cancer agents

Alhakamy,

Saquib,

Sanobar

et al. 2023

Front. Pharmacol.

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“…[28] Molecular hybridization is an important new strategy in medicinal chemistry and drug discovery that is based on the design of new chemical entities by the combination of two or more bioactive compounds or pharmacophoric units, as is evidenced by the large number of papers currently being published on this topic. [5,[42][43][44][45] These reports led us to envisage the development of a new chemical entity (NCE), by integrating neo-tanshinlactone and chalcone onto one template to obtain a biomimicking benzocoumarin-chalcone chimeric scaffold, in our search for a potent and selective new anti-breast cancer molecule (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Bioinspired Benzocoumarin‐Chalcones Chimeras as Potential Anti‐Breast Cancer Agents

et al. 2021

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The design and synthesis of a library of natural product inspired benzocoumarin-chalcones chimeras, as potent and selective, novel, anti-breast cancer scaffold, is reported herein. Twentyone new chimeric molecules, 25-45, were synthesized through an efficient protocol involving the Horner-Wadsworth-Emmonsolefination of β-aryl-β-ketophosphonates with 4-formyl-2Hbenzo[h]chromen-2-ones as the key step, and evaluated for anti-proliferative activity against a panel of four breast cancer and related cell lines viz. MDA-MB-231 (ER-ve), MCF-7 (ER + ve), Ishikawa (endometrial cancer) and Hela (cervical cancer). The synthesized molecules showed in vitro anti-proliferative activity in a range of 7.42 to 74.68 μM (IC 50 ). Compounds 33 and 34 showed very good activity, with 34 exhibiting better activity than the standard drugs, tamoxifen and raloxifene. Interestingly, none of the compounds showed cytotoxity against the normal human cell line. To identify the possible targets of the active compounds, molecular docking analysis was conducted to correlate their interaction with the ERα and ERβ receptors. From among the active compounds the docked conformations of 34, at the ERα and ERβ active sites, showed that it fits most favorably in the ligand binding space and shows hydrophobic interactions with the salient residues. Based on the above findings, 34 was identified as a lead molecule for development of more potent anti-breast cancer agents.

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“…15,16 And some sugar-pyrazole hybrids with good anticancer activity were reported recently. 17,18 It provided inspiration for us to develop more convenient and quickly method for novel sugar-based pyrazole derivatives with potential biological activity. The widely accepted synthetic way for acyl pyrazoles was the coupling of an appropriate hydrazide with corresponding 2, 4-pentanedione analogues.…”

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confidence: 99%

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Microwave-assisted rapid synthesis of sugar-based pyrazole derivatives with anticancer activity in water

Xia

Wei

et al. 2016

RSC Adv.

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Regioselective synthesis of densely functionalized, enantiopure, sugar–pyrazole hybrids as potential scaffolds for drug discovery

Cited by 10 publications

References 48 publications

Natural product-inspired synthesis of coumarin–chalcone hybrids as potential anti-breast cancer agents

Natural product-inspired synthesis of coumarin–chalcone hybrids as potential anti-breast cancer agents

Design and Synthesis of Bioinspired Benzocoumarin‐Chalcones Chimeras as Potential Anti‐Breast Cancer Agents

Microwave-assisted rapid synthesis of sugar-based pyrazole derivatives with anticancer activity in water

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