Structure-based design and synthesis of a novel long-chain 4′′-alkyl ether derivative of EGCG as potent EGFR inhibitor: <i>in vitro</i> and <i>in silico</i> studies

Singh, Satyam; Sahadevan, Revathy; Roy, Rajarshi; Biswas, Mainak; Ghosh, P. K.; Kar, Parimal; Sonawane, Avinash; Sadhukhan, Sushabhan

doi:10.1039/d2ra01919a

Cited by 14 publications

(28 citation statements)

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“…We examined the expression level of cleaved caspase-3. The intrinsic and extrinsic pathways are essential in activating the caspase cascade, a common characteristic biological feature during apoptosis. , We selected the obtained IC 50 values of C1 (15.01 μM), C2 (24.05 μM), GC1 (7.50 μM), and GC2 (10.17 μM) for the Western blot experiments. After exposing the HeLa cells to synthesized compounds for 24 h, Western blot results showed the cleavage of caspase-3 (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Chitosan–Biotin-Conjugated pH-Responsive Ru(II) Glucose Nanogel: A Dual Pathway of Targeting Cancer Cells and Self-Drug Delivery

Pragti,

Kundu,

Singh

et al. 2023

ACS Appl. Mater. Interfaces

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The current study paves the way for improved chemotherapy by creating pH-responsive nanogels (NGs) (GC1 and GC2) loaded with synthetic ruthenium(II) arene complexes to increase biological potency. NGs are fabricated by the conjugation of chitosan (CTS)–biotin biopolymers that selectively target the cancer cells as CTS has the pH-responsive property, which helps in releasing the drug in cancer cells having pH ∼ 5.5, and biotin provides the way to target the cancer cells selectively due to the overexpression of integrin. The synthesized compounds and NGs were thoroughly characterized using various spectroscopic and analytical techniques such as NMR, electrospray ionization-mass spectrometry, Fourier transform infrared, UV–vis, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, rheology, Brunauer–Emmett–Teller, and others. NGs displayed exceptional increased efficacy toward cancerous cells with IC50 values ranging from 7.50 to 18.86 μM via induced apoptosis in three human cancer cell lines. Apart from its potency, NGs were found to be highly selective toward cancer cells. Moreover, based on the results of immunoblot analysis, it was observed that the synthesized compounds exhibit a significant increase in the expression of cleaved caspase-3 and a decrease in the expression of the antiapoptotic protein BCL-XL. Interestingly, the complexes were discovered to have the additional capability of catalyzing the conversion of NADH to NAD+, leading to the generation of radical oxygen species within the cells. Additionally, it was discovered that NG-induced apoptosis depends on ROS production and DNA binding. A narrower range of LD50 values (1185.93 and 823.03 μM) was seen after administering NGs to zebrafish embryos in vivo. The results support the use of drug-loaded NGs as potential chemotherapeutic and chemopreventive agents for human cancer cells.

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Section: Resultsmentioning

confidence: 99%

Chitosan–Biotin-Conjugated pH-Responsive Ru(II) Glucose Nanogel: A Dual Pathway of Targeting Cancer Cells and Self-Drug Delivery

Pragti,

Kundu,

Singh

et al. 2023

ACS Appl. Mater. Interfaces

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“…54 Therefore, western blot experiments were carried out to explore the effects of ruthenium-based complexes on the expression of cleaved caspase-3. 55 The results obtained from immunoblot analysis strongly suggested that all three complexes remarkably upregulate the expression of cleaved caspase-3. However, compared to the control, complex 2 increases the cleaved caspase-3 expression most, followed by complex 1 and complex 3 .…”

Section: In Vitro Cell Viability Assaymentioning

confidence: 94%

Studies on anticancer properties with varying co-ligands in a Ru(ii) arene benzimidazole system

et al. 2023

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“…In silico methods are very useful in modeling epidemiology‐based data, identifying targeted therapies for novel drug design, repurposing drugs, predicting vaccine epitopes, and formulating diagnostic models for COVID‐19 35,36 . In addition, computational screening, such as molecular docking and MD simulations, can identify the significant roles of phytochemicals as adjuvants and assist in the selection of candidates for in vivo experiments 37 …”

Section: Introductionmentioning

confidence: 99%

“…35,36 In addition, computational screening, such as molecular docking and MD simulations, can identify the significant roles of phytochemicals as adjuvants and assist in the selection of candidates for in vivo experiments. 37 This computational study was carried out to investigate the interactions of Omicron SGp RBD from variants BA.1, BA.…”

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confidence: 99%

Computational studies on the interaction of Omicron subvariants (BA.1, BA.2, and BA.3) with ACE2 and polyphenols

Vardhan

Sahoo

2023

Phytochemical Analysis

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IntroductionThe SARS‐CoV‐2 Omicron variant BA.2 is spreading widely across the globe. The World Health Organization (WHO) designated BA.2 as a variant of concern due to its high transmission rate and pathogenicity. To elucidate the structural changes caused by mutations, we conducted a comparative analysis of BA.2 with variants BA.1 and BA.3.ObjectiveIn the present study, we aimed to investigate the interactions of the spike glycoprotein receptor‐binding domain (SGp RBD) of Omicron variants BA.1, BA.2, and BA.3 with the human receptor hACE2. Further, a library of 233 polyphenols was screened by molecular docking with the SGp RBDs of Omicron variants BA.1, BA.2, and BA.3.MethodsProtein–protein and protein–ligand molecular docking simulations were performed with AutoDock Vina and the ClusPro 2.0 server, respectively. The protein–ligand interactions were evaluated by BIOVIA Discovery Studio and ChimeraX 1.4. The molecular dynamics simulations for 100 ns were performed using GROMACS 2021.ResultsCompared to other variants of concern, the structural changes in Omicron caused by mutations at key positions improved its ability to cause infection. Despite multiple mutations, many important polyphenols bind effectively at the RBDs of Omicron variants, with the required pharmacokinetic and ADME features and obeying the Lipinski rule.ConclusionEven though Omicron variants have multiple mutations and their transmission rate is relatively high, the computed binding affinities of lead polyphenols like epigallocatechin‐3‐O‐gallate (EGCG) and luteolin‐7‐O‐glucuronide (L7G) indicate that traditional medicines and proper immunity booster diets may be useful in the long‐term fight against SARS‐CoV‐2.

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Structure-based design and synthesis of a novel long-chain 4′′-alkyl ether derivative of EGCG as potent EGFR inhibitor: in vitro and in silico studies

Abstract: Among the synthesized 4′′-alkyl EGCG derivatives, 4′′-C14 EGCG inhibited EGF stimulated phosphorylation of EGFR and its downstream signaling pathways, ERK and Akt. 4′′-C14 EGCG showed significantly improved stability than EGCG and induced apoptosis.

Cited by 14 publications

References 91 publications

Chitosan–Biotin-Conjugated pH-Responsive Ru(II) Glucose Nanogel: A Dual Pathway of Targeting Cancer Cells and Self-Drug Delivery

Chitosan–Biotin-Conjugated pH-Responsive Ru(II) Glucose Nanogel: A Dual Pathway of Targeting Cancer Cells and Self-Drug Delivery

Studies on anticancer properties with varying co-ligands in a Ru(ii) arene benzimidazole system

Computational studies on the interaction of Omicron subvariants (BA.1, BA.2, and BA.3) with ACE2 and polyphenols

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