The Thiadiazole Ring (THD) Is a Building Block for Potential Inhibitors of the SARS-CoV-2 Main Protease (Mpro): Theoretical Look into the Structure, Reactivity, and Binding Profile of Three 1,3,4-THD Derivatives toward Mpro DOI Creative Commons
Dileep C. Shanthakumar, T.N. Lohith, Bienfait Kabuyaya Isamura

et al.

Published: Dec. 21, 2023

Thiadiazole (THD) derivatives are famous for their exceptional chemical properties and versatile biological activities. In this work, we report computational investigations of the structure, reactivity, binding affinity three 1,3,4-THD (THDs) toward SARS-CoV-2 main protease (Mpro). Hirshfeld surface (HS) analyses carried out in conjunction with topological calculations context quantum theory atoms molecules (QTAIM) reduced density gradient (RDG) to unravel nature magnitude noncovalent interactions that contribute maintaining these THDs. The approaches consistently indicate titled THDs mainly stabilized by weak intramolecular H…H, C-H…π, C-H…N, N-H..H monomeric forms, while dimers also exhibit intermolecular π…π stacking T-shaped contacts. addition, atomic charges, frontier molecular orbitals (FMOs), Fukui functions, electrostatic potential (MEP) reveal pyrrolic H atom (ring F) imidazole N E) preferred sites nucleophilic electrophilic attacks, respectively. Finally, docking dynamics simulations demonstrate remarkable profile Mpro, which can be related inhibitory activity.

Language: Английский

Predictive Modelling in pharmacokinetics: from in-silico simulations to personalized medicine DOI
Ajita Paliwal, Smita Jain, Sachin Kumar

et al.

Expert Opinion on Drug Metabolism & Toxicology, Journal Year: 2024, Volume and Issue: 20(4), P. 181 - 195

Published: March 14, 2024

Pharmacokinetic parameters assessment is a critical aspect of drug discovery and development, yet challenges persist due to limited training data. Despite advancements in machine learning in-silico predictions, scarcity data hampers accurate prediction candidates' pharmacokinetic properties.

Language: Английский

Citations

8
In silico exploration of natural xanthone derivatives as potential inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and cellular entry DOI Creative Commons
Vincent A. Obakachi, Vaderament‐A. Nchiozem‐Ngnitedem, Krishna Govender

et al.

Journal of Computer-Aided Molecular Design, Journal Year: 2025, Volume and Issue: 39(1)

Published: Feb. 17, 2025

Language: Английский

Citations

0
Molecular Docking, DFT and Dynamics Simulations of Jatropha curcas-Derived Compounds Targeting PR and hERα for Breast Cancer Treatment DOI
Emmanuel Kitete Mulongo,

Jason Kilembe Thambwe,

N Y

et al.

Next research., Journal Year: 2025, Volume and Issue: unknown, P. 100249 - 100249

Published: March 1, 2025

Language: Английский

Citations

0
Evaluation of antiviral potential of Cinchona officinalis derived compounds against COVID-19 and Human hepatitis B: An in silico Molecular Docking and Molecular Dynamics Simulation study DOI
Emmanuel Kitete Mulongo, Aristote Matondo, Koto-te-Nyiwa Ngbolua

et al.

Pharmacological Research - Natural Products, Journal Year: 2025, Volume and Issue: unknown, P. 100229 - 100229

Published: April 1, 2025

Language: Английский

Citations

0
In vitro evaluation of curcumin's antisickling activity and in silico analysis of curcuminoids and their ADMET properties DOI Creative Commons
Clément M. Mbadiko, Koto-te-Nyiwa Ngbolua, Gédéon Ngiala Bongo

et al.

Discover Chemistry., Journal Year: 2025, Volume and Issue: 2(1)

Published: May 11, 2025

Language: Английский

Citations

0
SARS-CoV-2 Mpro binding profile and drug-likeness of two novel thiazole derivatives: structural elucidation, DFT studies, ADME-T and molecular docking simulations DOI
T.N. Lohith, Krishna Ravi Singh, Bienfait Kabuyaya Isamura

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2022, Volume and Issue: 41(20), P. 11122 - 11136

Published: Dec. 28, 2022

AbstractTwo novel thiazole derivatives, ethyl 5-((4-fluorophenyl)carbamoyl)-thiazole-4-carboxylate (2b) and 5-(p-tolylcarbamoyl)thiazole-4-carboxylate (6b) have been synthesized, their crystal structures determined by X-ray diffraction. To rationalize structure, reactivity druggability, we performed a series of separate, but complementary studies. Hirshfeld surface 2D-fingerprint plots were first scrutinized to qualitatively unveil all the intermolecular interactions that ensure packing. Moreover, topological electron density parameters established from quantum theory atoms-in-molecules (QTAIM) Reduced Density Gradient (RDG) later relied on characterize chemical bonding these species, in terms nature magnitude noncovalent developed within monomeric dimeric forms. In both structures, C-H…O hydrogen bonds are found be stronger than other interactions. Furthermore, H…H contacts non-conventional C–H…O exhibit closed shell nature, play crucial role stability thiazoles. The isosurfaces region furnished NCI molecular diagram signifies existence weak Finally, potential inhibitory activity titled compounds drug-likeness demonstrated docking ADME-T calculations respectively. Both adhere Lipinski's rule five present encouraging pharmacokinetic properties safety profiles.Communicated Ramaswamy H. SarmaKeywords: Thiazolestructure elucidationDFTdockingADME-T AcknowledgmentAuthors thankful IIT Madras for collecting intensity data. K. Ravi Singh, thanks IoE, Vijnana Bhavan, University Mysore, financial support. B.K. Isamura is grateful Prof Kevin Lobb having provided access 'carbon' cluster at Rhodes University.Disclosure statementNo conflict interest was reported author(s).

Language: Английский

Citations

15
Molecular docking and molecular dynamics simulation studies of the interaction of anti-oral cancer plant Curcuma longa derived-compounds with human epidermal growth factor receptor 2 DOI

Mfutu Mana Charly,

Koto-te-Nyiwa Ngbolua,

Jean-Paul Sekele Issouradi

et al.

Journal of Proteins and Proteomics, Journal Year: 2024, Volume and Issue: 15(3), P. 491 - 507

Published: July 16, 2024

Language: Английский

Citations

3
Design, Synthesis, and Biological Studies of C-5-Substituted Diazenyl Derivatives of Uracil as Potent and Selective Antileishmanial Agents Targeting Uridine Biosynthesis Pathway Enzymes DOI
Tushar Kanti Das, Prakash Kumar, Sachin Kumar

et al.

ACS Infectious Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Herein, we describe the design and synthesis of a series C-5-substituted diazenyl derivatives uracil, exhibiting selective potent antileishmanial but not antibacterial or antifungal activity. The formation substituted was confirmed by using FTIR,

Language: Английский

Citations

2
Repurposing and computational design of PARP inhibitors as SARS-CoV-2 inhibitors DOI Creative Commons
Shailima Rampogu, Tae Sung Jung, Min Woo Ha

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: June 29, 2023

Coronavirus disease 2019 (COVID-19) is a recent pandemic that caused serious global emergency. To identify new and effective therapeutics, we employed drug repurposing approach. The poly (ADP ribose) polymerase inhibitors were used for this purpose repurposed against the main protease (Mpro) target of severe acute respiratory syndrome 2 (SARS-CoV-2). results from these studies to design compounds using 'Grow Scaffold' modules available on Discovery Studio v2018. three designed compounds, olaparib 1826 1885, rucaparib 184 demonstrated better CDOCKER docking scores Mpro than their parent compounds. Moreover, adhered Lipinski's rule five synthetic accessibility score 3.55, 3.63, 4.30 1826, 184, respectively. short-range Coulombic Lennard-Jones potentials also support potential binding modified Mpro. Therefore, propose as novel SARS-CoV-2 inhibitors.

Language: Английский

Citations

6
Antiviral activities of olive oil apigenin and taxifolin against SARS-CoV-2 RNA-dependent RNA polymerase (RdRP): In silico , pharmacokinetic, ADMET, and in-vitro approaches DOI Creative Commons
Samy Selim, Mha Albqmi, Awadh Alanazi

et al.

Cogent Food & Agriculture, Journal Year: 2023, Volume and Issue: 9(1)

Published: July 29, 2023

A novel coronavirus strain called SARS-CoV-2 first appeared in China December 2019. Natural products are significant sources of prospective and new antiviral medications, drug research has advanced significantly recent years. The current study allows us to select specific components olive oil that thought be anti-SARS-CoV-2 assess their impact on vitro. 26 compounds were obtained from the PubChem database docked against RdRP (pdb id: 6XQB) by autodock vina 1 2 linux x86 software. Cytotoxicity activity measured MTT assay protocol (the crystal violet method). findings revealed range compound's molecular docking binding affinity score target was 5.9–18.2 kcal/mol. best compound is apigenin since it a low energy value −18.2 kcal/mol, followed taxifolin, which an −14.2 On other hand, molecule with lowest believed good one. Additionally, Lipinski's criteria AD-MET analysis supported created taxifolin's status as secure pharmaceutical substance. Also, taxifolin showed moderate effectiveness vitro, SI values 9.7 8.79, respectively, compared oil's crude 9.57. According our results, we think essential source cutting-edge drugs, especially compounds.

Language: Английский

Citations

4