Molecular structure, NBO analysis of the hydrogen-bonded interactions, spectroscopic (FT–IR, FT–Raman), drug likeness and molecular docking of the novel anti COVID-2 molecule (2E)-N-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide (Dimer) - quantum chemical approach

Mary, S. J. Jenepha; Pradhan, Sayantan; James, C.

doi:10.1016/j.saa.2020.119388

Cited by 14 publications

(8 citation statements)

References 69 publications

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“…Furthermore, second-order perturbation theory analysis of the Fock matrix in NBO basis revealed that the interaction between the lone pair of O and H b in 12 (interaction energy: 5.41 kcal/mol) is stronger than the interaction between the lone pair of O and hydrogen atoms H a and H b in 11 (interaction energy: 1.12 and 0.56 kcal/mol, respectively). This interaction energy is indicative of a charge-transfer interaction between the H-atom and the O-atom …”

Section: Resultsmentioning

confidence: 99%

Discovery of an Oral, Beyond-Rule-of-Five Mcl-1 Protein–Protein Interaction Modulator with the Potential of Treating Hematological Malignancies

et al. 2023

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Avoidance of apoptosis is critical for the development and sustained growth of tumors. The pro-survival protein myeloid cell leukemia 1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 family of proteins which is overexpressed in many cancers. Upregulation of Mcl-1 in human cancers is associated with high tumor grade, poor survival, and resistance to chemotherapy. Therefore, pharmacological inhibition of Mcl-1 is regarded as an attractive approach to treating relapsed or refractory malignancies. Herein, we disclose the design, synthesis, optimization, and early preclinical evaluation of a potent and selective small-molecule inhibitor of Mcl-1. Our exploratory design tactics focused on structural modifications which improve the potency and physicochemical properties of the inhibitor while minimizing the risk of functional cardiotoxicity. Despite being in the "non-Lipinski" beyond-Rule-of-Five property space, the developed compound benefits from exquisite oral bioavailability in vivo and induces potent pharmacodynamic inhibition of Mcl-1 in a mouse xenograft model.

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Section: Resultsmentioning

confidence: 99%

Discovery of an Oral, Beyond-Rule-of-Five Mcl-1 Protein–Protein Interaction Modulator with the Potential of Treating Hematological Malignancies

et al. 2023

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“…It exhibited H-bonding interactions with amino acid residues CYS-145A; van der Waals interactions with residues TYR-54A, ASN-142A, SER-144A, HIS-164A, GLU-166A, ASP-187A, ARG-188A, GLN-189A, LEU-141A, and GLY-143A; hydrophobic interactions with PRO-52A, MET-49A, and HIS-41; and Pi-sulfur interactions with residue MET-165A. Mary et al, 111 synthesized N -methyl-2-[(4-oxo-4 H -chromen-3-yl)methylidene]-hydrazinecarbothioamide (MCMH) and evaluated its anti-COVID-19 activity using in silico studies. Compound (MCMH) 88 exhibited the highest binding affinity towards the main protease (M pro ) (PDB code: 5r80) of SARS-CoV-2, with a docking score of −8.8kcal/mol.…”

Section: In Silico Studies Of Covid-19mentioning

confidence: 99%

A Comprehensive Update of Anti-COVID-19 Activity of Heterocyclic Compounds

Nazir,

Ahmad,

Aslam

et al. 2024

DDDT

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The Coronavirus disease 2019 (COVID-19) pandemic is one of the most considerable health problems across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the major causative agent of COVID-19. The severe symptoms of this deadly disease include shortness of breath, fever, cough, loss of smell, and a broad spectrum of other health issues such as diarrhea, pneumonia, bronchitis, septic shock, and multiple organ failure. Currently, there are no medications available for coronavirus patients, except symptom-relieving drugs. Therefore, SARS-CoV-2 requires the development of effective drugs and specific treatments. Heterocycles are important constituents of more than 85% of the physiologically active pharmaceutical drugs on the market now. Several FDA-approved drugs have been reported including molnupiravir, remdesivir, ritonavir, oseltamivir, favipiravir, chloroquine, and hydroxychloroquine for the cure of COVID-19. In this study, we discuss potent anti-SARS-CoV-2 heterocyclic compounds that have been synthesized over the past few years. These compounds included; indole, piperidine, pyrazine, pyrimidine, pyrrole, piperazine, quinazoline, oxazole, quinoline, isoxazole, thiazole, quinoxaline, pyrazole, azafluorene, imidazole, thiadiazole, triazole, coumarin, chromene, and benzodioxole. Both in vitro and in silico studies were performed to determine the potential of these heterocyclic compounds in the fight against various SARS-CoV-2 proteins.

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“…Flavonoids are phytochemicals that give plants their characteristic colors and occur naturally in plants' seeds, owers, fruits, leaves, and bark. They represent the most common phenolics in plants and constitute a broad class of compounds divided into various subclasses, such as anthocyanins, avanones, iso avones, avones, avanols (catechins), chalcones, and avonols based on variations in their fundamental structure [9][10][11] . Flavonoids possess biological and oxidative properties that contribute to their anti-allergic, cardioprotective, anti-diabetic, anti-in ammatory, anti-oxidative, and free radical scavenging actions 9 .…”

Section: Introductionmentioning

confidence: 99%

“…Flavonoids possess biological and oxidative properties that contribute to their anti-allergic, cardioprotective, anti-diabetic, anti-in ammatory, anti-oxidative, and free radical scavenging actions 9 . Many avonoids have a chromone structure, which is widely distributed in nature, particularly in the plant kingdom, and exhibit pharmacological activity against in uenza, hepatitis B, human rhinovirus (HRV), and neurodegenerative diseases 10 . Chromones have a benzene ring's 5-and 6-positions fused with the c-pyrone nucleus.…”

Section: Introductionmentioning

confidence: 99%

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Investigating the Potential of 6-Substituted 3-Formyl Chromone Derivatives as Anti-Diabetic Agents Using DFT, Molecular Docking and Molecular Dynamics Methods

Saif,

Esha,

Quayum

et al. 2023

Preprint

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The focus of this research is to investigate the potential of 6-substituted 3-formyl chromone derivatives (1-16) for various biological activities such as antifungal, antiviral, antibacterial, antiallergenic etc. The research examined the formyl group at the chromone’s C-3 position. ADMET, biological activities, were conducted along with B3LYP calculations using 3 different basis sets. The analogues were analyzed based on their parent structure obtained from PubChem. The HOMO-LUMO gap confirmed the bioactive nature of the derivatives, NBO analysis was performed to understand the charge transfer. PASS prediction revealed that 3-formyl chromone derivatives are potent aldehyde oxidase inhibitors, insulin inhibitors, HIF1A expression inhibitors, and histidine kinase. Molecular docking studies indicated that the compounds had a strong binding affinity with proteins, including CAD, BHK, IDE, HIF-α, p53, COX, and Mpro of SARS-CoV2. 6-isopropyl-3-formyl chromone (4) displayed the highest affinity for IDE, with a binding energy of -8.5 kcal mol⁻¹. This result outperformed the affinity of the reference standard dapagliflozin (-7.9 kcal mol⁻¹) as well as two other compounds that target human IDE, namely vitexin (-8.3 kcal mol⁻¹) and myricetin (-8.4 kcal mol⁻¹). MD simulations were revealed RMSD value between 0.2 and 0.5 nm, indicating the strength of the protein-ligand complex at the active site.

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Molecular structure, NBO analysis of the hydrogen-bonded interactions, spectroscopic (FT–IR, FT–Raman), drug likeness and molecular docking of the novel anti COVID-2 molecule (2E)-N-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide (Dimer) - quantum chemical approach

Cited by 14 publications

References 69 publications

Discovery of an Oral, Beyond-Rule-of-Five Mcl-1 Protein–Protein Interaction Modulator with the Potential of Treating Hematological Malignancies

Discovery of an Oral, Beyond-Rule-of-Five Mcl-1 Protein–Protein Interaction Modulator with the Potential of Treating Hematological Malignancies

A Comprehensive Update of Anti-COVID-19 Activity of Heterocyclic Compounds

Investigating the Potential of 6-Substituted 3-Formyl Chromone Derivatives as Anti-Diabetic Agents Using DFT, Molecular Docking and Molecular Dynamics Methods

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