Pyridazin-3(2H)-one Derivatives: Computational ADME-Tox, Molecular Docking, Drug-Likeness Analysis, Molecular Dynamics Simulations, and Assessment of Their Antitubercular Potential

Mohamed El Bouamri; Badr Gourmah; Amine Bayen; Osama Zehloul; Mohamed Yafout; Walid Ziraoui; Amal Ait Haj Said; Adnane Benmoussa

doi:10.18596/jotcsa.1971306

Pyridazin-3(2H)-one Derivatives: Computational ADME-Tox, Molecular Docking, Drug-Likeness Analysis, Molecular Dynamics Simulations, and Assessment of Their Antitubercular Potential

Abstract

Pyridazinones are a versatile class of heterocycles that have been gaining interest in the field of antimicrobial compound development. In the present study, an integrated in silico workflow has been developed for the assessment and prioritization of a small dataset of novel pyridazinones as promising antitubercular compounds against Mycobacterium tuberculosis, recently synthesized and reported in 2025. Molecular docking studies demonstrated favorable binding interactions within the active site of the target protein, with several newly designed derivatives surpassing the binding affinity of the co-crystallized native ligand (-9.6 kcal/mol) and reaching docking energies of up to -11.4 kcal/mol. Subsequent drug-likeness assessment according to Lipinski’s Rule of Five, coupled with ADMET profiling, highlighted compounds 18 and 22 as the most promising candidates, owing to their predicted oral bioavailability, desirable pharmacokinetic characteristics, and favorable toxicity profile. Nevertheless, further 100 ns molecular dynamics simulations and MM/GBSA free energy evaluations rectified the initial static scoring, confirming Compound 22 as the true lead candidate with optimized interactions in the 5V3X binding pocket. The 5V3X-22 complex exhibited high stability, maintaining a steady backbone RMSD of about 0.2 nm, stable ligand RMSD, and key hydrogen bonding interactions throughout the simulation, alongside a conserved radius of gyration and SASA value. According to the MM/GBSA approach, it was possible to conclude that the binding energy of compound 22 is higher and more consistent than that of compound 18 due to increased Van der Waals interactions. Summing up, computational research allowed us to define compound 22 as the most effective potential lead in the series and prepare for in vitro validation of its activity against M. tuberculosis.

Keywords

References

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Details

Primary Language

English

Subjects

Natural Products and Bioactive Compounds, Biomolecular Modelling and Design

Journal Section

Research Article

Authors

Mohamed El Bouamri ^*
0009-0002-6553-3740
Morocco

Badr Gourmah
0009-0005-7147-3475
Morocco

Amine Bayen
0009-0002-4601-3547
Morocco

Osama Zehloul
0009-0005-5129-4269
Morocco

Mohamed Yafout
0000-0002-8936-8092
Morocco

Walid Ziraoui
0009-0005-7058-1167
Morocco

Amal Ait Haj Said
0000-0003-4996-8410
Morocco

Adnane Benmoussa
0000-0002-1037-7819
Morocco

Publication Date

November 5, 2026

Submission Date

June 15, 2026

Acceptance Date

September 26, 2026

Published in Issue

Year 2026 Volume: 2026 Number: 2

DOI

https://doi.org/10.18596/jotcsa.1971306

IZ

https://izlik.org/JA79SB62ZM

Cite

RIS / Bibtex

APA

El Bouamri, M., Gourmah, B., Bayen, A., Zehloul, O., Yafout, M., Ziraoui, W., Ait Haj Said, A., & Benmoussa, A. (2026). Pyridazin-3(2H)-one Derivatives: Computational ADME-Tox, Molecular Docking, Drug-Likeness Analysis, Molecular Dynamics Simulations, and Assessment of Their Antitubercular Potential. Journal of the Turkish Chemical Society Section A: Chemistry, 2026(2), 1-24. https://doi.org/10.18596/jotcsa.1971306

AMA

1.El Bouamri M, Gourmah B, Bayen A, et al. Pyridazin-3(2H)-one Derivatives: Computational ADME-Tox, Molecular Docking, Drug-Likeness Analysis, Molecular Dynamics Simulations, and Assessment of Their Antitubercular Potential. JOTCSA. 2026;2026(2):1-24. doi:10.18596/jotcsa.1971306

Chicago

El Bouamri, Mohamed, Badr Gourmah, Amine Bayen, et al. 2026. “Pyridazin-3(2H)-One Derivatives: Computational ADME-Tox, Molecular Docking, Drug-Likeness Analysis, Molecular Dynamics Simulations, and Assessment of Their Antitubercular Potential”. Journal of the Turkish Chemical Society Section A: Chemistry 2026 (2): 1-24. https://doi.org/10.18596/jotcsa.1971306.

EndNote

El Bouamri M, Gourmah B, Bayen A, Zehloul O, Yafout M, Ziraoui W, Ait Haj Said A, Benmoussa A (November 1, 2026) Pyridazin-3(2H)-one Derivatives: Computational ADME-Tox, Molecular Docking, Drug-Likeness Analysis, Molecular Dynamics Simulations, and Assessment of Their Antitubercular Potential. Journal of the Turkish Chemical Society Section A: Chemistry 2026 2 1–24.

IEEE

[1]M. El Bouamri et al., “Pyridazin-3(2H)-one Derivatives: Computational ADME-Tox, Molecular Docking, Drug-Likeness Analysis, Molecular Dynamics Simulations, and Assessment of Their Antitubercular Potential”, JOTCSA, vol. 2026, no. 2, pp. 1–24, Nov. 2026, doi: 10.18596/jotcsa.1971306.

ISNAD

El Bouamri, Mohamed - Gourmah, Badr - Bayen, Amine - Zehloul, Osama - Yafout, Mohamed - Ziraoui, Walid - Ait Haj Said, Amal - Benmoussa, Adnane. “Pyridazin-3(2H)-One Derivatives: Computational ADME-Tox, Molecular Docking, Drug-Likeness Analysis, Molecular Dynamics Simulations, and Assessment of Their Antitubercular Potential”. Journal of the Turkish Chemical Society Section A: Chemistry 2026/2 (November 1, 2026): 1-24. https://doi.org/10.18596/jotcsa.1971306.

JAMA

1.El Bouamri M, Gourmah B, Bayen A, Zehloul O, Yafout M, Ziraoui W, Ait Haj Said A, Benmoussa A. Pyridazin-3(2H)-one Derivatives: Computational ADME-Tox, Molecular Docking, Drug-Likeness Analysis, Molecular Dynamics Simulations, and Assessment of Their Antitubercular Potential. JOTCSA. 2026;2026:1–24.

MLA

El Bouamri, Mohamed, et al. “Pyridazin-3(2H)-One Derivatives: Computational ADME-Tox, Molecular Docking, Drug-Likeness Analysis, Molecular Dynamics Simulations, and Assessment of Their Antitubercular Potential”. Journal of the Turkish Chemical Society Section A: Chemistry, vol. 2026, no. 2, Nov. 2026, pp. 1-24, doi:10.18596/jotcsa.1971306.

Vancouver

1.Mohamed El Bouamri, Badr Gourmah, Amine Bayen, Osama Zehloul, Mohamed Yafout, Walid Ziraoui, Amal Ait Haj Said, Adnane Benmoussa. Pyridazin-3(2H)-one Derivatives: Computational ADME-Tox, Molecular Docking, Drug-Likeness Analysis, Molecular Dynamics Simulations, and Assessment of Their Antitubercular Potential. JOTCSA. 2026 Nov. 1;2026(2):1-24. doi:10.18596/jotcsa.1971306

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We are using Intihal.net (formerly, we used iThenticate) plagiarism software and our maximum allowed score for the document is, depending on the conditions of the article, about 20-25%. We look at the document and if we see a pattern of plagiarism, we return the document. If not, we continue the process. In cases with high similarity, it is recommended that the author works with article editing firms to lower the score. In this case, a language editing certificate is handy. A single similarity index cannot be higher than 5%, please reduce the similarity of a given entity less than 5%.

Please do not submit PDF copies of your articles for preliminary control. We accept Microsoft Word DOC, Microsoft Word DOCX, and LibreOffice ODT. We directly work on the manuscript, forming changes that are trackable.

Please do not submit your work again from the very beginning, if the management requires that you prepare a revision. Just browse to your existing submission and use the upload module to upload the newer version. If you are stuck, please send the revised article with an e-mail to the managing editor at jotcsa@turchemsoc.org.

Our journal will use, beginning from 10(1), a manual heading-based system with numbers, like 1. INTRODUCTION, 2.1. Materials and Methods, etc. More information will be found in the template file.

You may download the article templates, depending on your word processor, from the link below. Kindly recall that we do not have any LaTeX templates for now:

📝 article_template_word.docx
(please contact the editorial office at jotcsa@turchemsoc.org for open document, ODT, form of this file).

📝 APC_CONSENT_FORM.docx

*Potential reviewer recommendation form

Reaction schemes usually used for reactions and related material will use Arial or Verdana, preferably at 9 or 10 points, inside the figures. Our journal recommends that authors use "Chemdraw" or "ChemSketch" or "MarvinSketch" softwares. Directly pasting from the drawing application into the word processor software is NOT recommended. Please use the "paste special" feature to paste it as a metafile image.

Citing: Our journal uses a number-based reference system, and the number is given in normal parenthesis like (17). Other examples include (1-3, 17), (1-3, 17, 19-21), etc. The above-mentioned reference managers have the required tools to create citations in the text. When inserting a new paragraph, the manager will safely rearrange the citations, refreshing the numbers.

For presentation of proton or carbon nuclear magnetic resonance data, please see the article template above.

The words Scheme 1, Figure 1, etc., will have a full stop at the end of the caption. The caption text will be centered on the page.

Supplementary information: The authors are encouraged to use supplementary information, for detailing the study with spectral data, crystal structure refinement data, and other types of material should you recommend including. All types of synthetic procedures will be included in the main text. Supplementary files will be added as a new file by the editors.

Usage of the units: The units will be, where possible, SI-based and the style g/mL will be preferred over g.mL-1. Please do not mix these two and apply consistency throughout the manuscript about using the units.

1. Publication Ethics

The Journal of the Turkish Chemical Society Section A: Chemistry (JOTCSA) is committed to maintaining the highest standards of publication ethics and follows the principles and best practice guidelines of the Committee on Publication Ethics (COPE). All parties involved in the publication process—including authors, editors, reviewers, and the publisher—are expected to adhere to these ethical standards.

The journal does not tolerate plagiarism, data fabrication, data falsification, duplicate publication, inappropriate authorship, or any other form of research or publication misconduct. Suspected ethical violations are handled in accordance with COPE guidelines.

2. Editorial Responsibilities

The Editor-in-Chief has overall responsibility for the editorial management of the journal. Manuscripts are assigned to Section Editors (please see the Editorial Board page for details), who oversee the peer-review process and make recommendations based solely on scientific merit.

Editors evaluate submissions objectively without discrimination based on race, gender, nationality, institutional affiliation, or personal beliefs. Editorial decisions are based on originality, scientific quality, methodological soundness, ethical compliance, and relevance to the journal's scope.

Editors maintain the confidentiality of submitted manuscripts and avoid handling manuscripts in which they have conflicts of interest.

3. Author Responsibilities

Authors are responsible for submitting original research that has not been published previously and is not under consideration elsewhere.

All listed authors must have made substantial scientific contributions to the work and approve the final version of the manuscript before submission.

Authors are responsible for the accuracy of the data presented and must disclose any financial or non-financial conflicts of interest. Any errors identified after publication should be reported promptly to the editorial office.

4. Reviewer Responsibilities

Reviewers provide independent, objective, and constructive evaluations of submitted manuscripts.

Reviewers should accept review invitations only when they have the appropriate expertise and can complete the review within the requested timeframe. Manuscripts under review must be treated as confidential documents.

Reviewers should disclose any potential conflicts of interest and decline the review if such conflicts could affect their impartiality.

5. Peer Review Process

JOTCSA operates a double-blind external peer-review system.

Following an initial editorial screening, each manuscript is assigned by the Editor-in-Chief to a Section Editor, who manages the peer-review process.

The Section Editor invites at least two independent external reviewers with expertise in the manuscript's subject areas. Reviewers are selected based on their scientific expertise and must have no conflicts of interest with the authors. Reviewers are not selected from the same institution as the corresponding author whenever possible.

The Section Editor oversees the review process but does not normally act as a reviewer. Editorial decisions are based on reviewers' reports, the editor's evaluation, and the scientific quality of the manuscript.

Possible editorial decisions include:

Accept
Minor Revision
Major Revision
Reject

6. Research Ethics (Human & Animal Studies)

Research involving human participants or animals must comply with internationally accepted ethical standards and applicable national regulations.

Studies involving human participants must have received approval from an appropriate ethics committee and be conducted in accordance with the Declaration of Helsinki. Informed consent must be obtained where applicable.

Studies involving animals must have received approval from the relevant institutional animal ethics committee and comply with internationally recognized guidelines for animal welfare.

Authors should provide ethics approval information within the manuscript.

7. Conflicts of Interest

Authors, editors, and reviewers must disclose any financial, professional, or personal relationships that could influence the objectivity of the publication process.

Authors should include a Conflict of Interest Statement in their manuscripts. If no conflicts exist, authors should state:

The authors declare no conflict of interest.

Editors and reviewers with conflicts of interest will not participate in the editorial or peer-review process for the affected manuscript.

8. Plagiarism and Similarity Checks

All submitted manuscripts undergo similarity screening using plagiarism detection software before peer review.

Similarity reports are evaluated by the editorial team. A similarity score alone does not determine editorial decisions; editors assess the nature, extent, and context of any textual overlap.

Manuscripts containing plagiarism, duplicate publication, manipulated images, or other forms of publication misconduct will be rejected or, if already published, handled according to COPE recommendations.

9. Corrections, Retractions and Expressions of Concern

The journal follows COPE recommendations for post-publication corrections.

Corrections may be published when errors affecting the accuracy or clarity of a published article are identified.

Retractions are issued when findings are shown to be unreliable due to major errors or research misconduct, including fabrication, falsification, plagiarism, duplicate publication, or unethical research.

Expressions of Concern may be published when serious concerns arise regarding a published article but conclusive evidence is not yet available.

All corrections, retractions, and editorial notices are permanently linked to the original article to maintain the integrity of the scholarly record.

10. Copyright & Licensing

Authors retain copyright of their published work.

Articles published in JOTCSA are distributed under the Creative Commons Attribution–NonCommercial–NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.

This license permits users to copy and redistribute the material in any medium or format for non-commercial purposes, provided appropriate credit is given to the original authors and source, no modifications are made, and the license terms are respected.

Editor-in-Chief

Hasan KÜÇÜKBAY

Organic Chemistry

Section Editor: Analytical Chemistry

F. Zehra KÜÇÜKBAY

Pharmaceutical Analytical Chemistry, Analytical Spectrometry, Instrumental Methods, Separation Science

Section Editor: Biochemistry

ST

Sevim TUNALI

Medicinal and Biomolecular Chemistry (Other)

Simla OLĞAÇ

Pharmacology and Pharmaceutical Sciences, Pharmaceutical Biochemistry, Molecular Medicine

Section Editor: Computational Chemistry

Fatih Mehmet AVCU

Deep Learning, Supervised Learning, Machine Learning Algorithms, Analytical Chemistry, Analytical Spectrometry, Theoretical and Computational Chemistry

Houssem BOULEBD

Organic Chemical Synthesis, Free Radical Chemistry, Computational Chemistry

Tugba TAŞKIN TOK

Bioinformatics and Computational Biology, Pharmaceutical Chemistry, Bioinorganic Chemistry, Nanochemistry, Organic Chemistry, Natural Products and Bioactive Compounds, Theoretical and Computational Chemistry (Other), Medicinal and Biomolecular Chemistry, Biomolecular Modelling and Design

Section Editor: Crystallography

Sibel Demir KANMAZALP

Molecular Docking, Condensed Matter Modelling and Density Functional Theory, Crystallography, Physical Organic Chemistry, Computational Chemistry, Theoretical and Computational Chemistry (Other)

Section Editor: Electrochemistry

Yücel KADIOGLU

Pharmaceutical Analytical Chemistry, Analytical Spectrometry, Instrumental Methods, Metabolomic Chemistry

Section Editor: Food Chemistry

Özge SÜFER

Food Sciences, Food Chemistry and Food Sensory Science, Grain Technology, Drying Technologies, Basic Food Processes

Section Editor: Forensic Chemistry

Orhan DESTANOĞLU

Analytical Spectrometry, Instrumental Methods, Quality Assurance, Chemometrics, Traceability and Metrological Chemistry, Analytical Chemistry (Other), Forensic Chemistry

Section Editor: Inorganic Chemistry

Dursun Ali KÖSE

Chemical Sciences, Inorganic Chemistry, Non-Metal Chemistry, Main Group Metal Chemistry, Bioinorganic Chemistry, F-Block Chemistry, Transition Metal Chemistry, Inorganic Green Chemistry, Solid State Chemistry, Crystallography, Metal Cluster Chemistry, Metal Organic Frameworks, Inorganic Chemistry (Other), Forensic Chemistry, Water Treatment Processes

Section Editor: Organic Chemistry

Davit JISHKARIANI

Nanochemistry, Supramolecular Chemistry, Organic Chemical Synthesis, Materials Science and Technologies

FC

Fabrizio CARTA

Characterisation of Biological Macromolecules, Biologically Active Molecules, Medicinal and Biomolecular Chemistry (Other), Health Sciences

Melike KALKAN

Analytical Spectrometry, Catalysis and Mechanisms of Reactions, Organic Chemistry

Hasan KÜÇÜKBAY

Organic Chemistry

Section Editor: Pharmaceutical chemistry

Anıl YILMAZ

Pharmacognosy, Pharmaceutical Chemistry, Natural Products and Bioactive Compounds, Organic Chemical Synthesis, Medicinal and Biomolecular Chemistry (Other)

Manisha PATIL

Pharmaceutical Chemistry

Section Editor: Photochemistry

Baybars KÖKSOY

Photochemistry, Organic Chemistry

Mücahit ÖZDEMIR

Chemical Sciences, Inorganic Chemistry (Other)

Section Editor: Physical Chemistry

Sinem GOKTURK

Chemical Sciences, Analytical Spectrometry, Physical Chemistry, Solution Chemistry, Colloid and Surface Chemistry, Reaction Kinetics and Dynamics, Physical Chemistry (Other)