Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.7
4.8
Journals
Pharmaceuticals
Special Issues
Synthesis, In Silico Prediction and Antitumor Activity of Nitrogen Heterocycle-Based...
share announcement

Synthesis, In Silico Prediction and Antitumor Activity of Nitrogen Heterocycle-Based Drug Development

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 25 October 2026 | Viewed by 1825

Special Issue Editors

Prof. Dr. Jamerson F. De Oliveira

E-Mail Website
Guest Editor
Institute of Health Sciences, University of International Integration of Afro-Brazilian Lusophony (UNILAB), Redenção 62790-970, CE, Brazil
Interests: privileged structures; nitrogen heterocycles; ADMET prediction; cancer biological target; molecular dynamic; computational studies; antitumor activity; in vitro and in vivo studies; SAR of lead compounds; molecular hybridization
Dr. Paulo André Teixeira de Moraes Gomes

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife 50740-521, Pernambuco, Brazil
Interests: privileged structures; nitrogen heterocycles; ADMET prediction; cancer biological target; molecular dynamic; computational studies; antitumor activity; in vitro and in vivo studies; SAR of Lead compounds; molecular hybridization

Special Issue Information

Dear Colleagues,

Privileged structures are molecular fragments found in lead and they present compounds of interest in medicinal chemistry. They play an important role since they can interact with several molecular targets of clinical importance and serve as a starting point for the design of new candidate drug structures. In this context, heterocycle compounds stand out as privileged structures and serve as scaffolds for the design of new drugs. These structures are present in compounds of natural origin, which serve as a basis for the synthesis of new molecules in amino acids such as proline, tryptophan, and histidine, which are essential for the interaction of drugs at the active site of many pharmacological targets. Additional emphasis is given to nitrogen heterocycles in view of FDA-approved antitumor drugs such as Almonertinib, Tivozanib, Zanubrutinib, and prototype antitumor agents. These structures can form important hydrogen bonds between the nitrogen atom and important points in biological cancer targets, forming more stable complexes. In addition, the presence of heterocycles can improve pharmaceutical and pharmacokinetic characteristics by altering parameters related to ADMET.In this Special Issue, we aim to bring together research from experts in the field that highlights the synthesis and in vitro and/or in vivo antitumor evaluation of new compounds containing fragments of nitrogenous heterocycles, as well as computational pharmacokinetic and/or pharmacodynamic studies that may contribute to the discovery and development of new antitumor agents.

Prof. Dr. Jamerson F. De Oliveira
Dr. Paulo André Teixeira de Moraes Gomes
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • privileged structures
  • nitrogen heterocycles
  • ADMET prediction
  • cancer biological target
  • molecular dynamic
  • computational studies
  • antitumor activity
  • in vitro and in vivo studies
  • SAR of lead compounds
  • molecular hybridization

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

30 pages, 3283 KB  
Article
Biological and Teratogenic Evaluations of Nitrogen Heterocycles for Anticancer Therapy
by Jéssica Celerino dos Santos, Josival Emanuel Ferreira Alves, Rafael David Souto de Azevedo, Josefa Gerlane da Silva, Maria Regina de Oliveira Silva, Lucia Patrícia Bezerra Gomes da Silva, Caio Victor Silva Soares, Jamire Muriel da Silva, Nabuêr Francieli da Silva, Jamerson Ferreira de Oliveira, Maria do Carmo Alves de Lima, Ricardo Olímpio de Moura and Sinara Mônica Vitalino de Almeida
Pharmaceuticals 2026, 19(3), 405; https://doi.org/10.3390/ph19030405 - 1 Mar 2026
Viewed by 740
Abstract
Background: Heterocycle compounds with acridine, quinoline, indole, and pyridine nuclei are potentially active for anticancer activity since they can promote inhibition of vital enzymes, decreasing cell survival after binding to biomolecules. However, unspecific biological interactions can result in unwanted effects, which should [...] Read more.
Background: Heterocycle compounds with acridine, quinoline, indole, and pyridine nuclei are potentially active for anticancer activity since they can promote inhibition of vital enzymes, decreasing cell survival after binding to biomolecules. However, unspecific biological interactions can result in unwanted effects, which should be defined during the synthesis and proposition of new molecules. Thus, the objective of this study was to investigate the biological and teratogenic effects of four nitrogen heterocycles proposed for anticancer therapy. Methods: Four 2-cyano-N-phenylacrylamine type derivatives containing acridine (3a), quinoline (3b), indole (3c), and pyridine (3d) nuclei were synthesized and characterized. They were evaluated for their ability to interact with DNA, physicochemical and pharmacokinetic predictions, in vitro and in silico methodologies, besides in vitro inhibition of the Topoisomerase IIα enzyme, antiproliferative activity in tumor and non-tumor cells, hemolytic activity with human erythrocytes, and in vivo toxicological studies with zebrafish embryos. Results: UV–vis absorption studies with ssDNA revealed different spectroscopic effects, with binding constants (Kb) ranging from 1.41 × 105 to 6.46 × 104 M−1. The fluorescence quenching constant (Ksv) with ethidium bromide (EB) varied between 0.53 and 0.67 × 103 M−1. The compounds intercalated into DNA base pairs, a mechanism confirmed by molecular docking, with 3b (quinoline) showing the most substantial interaction. All derivatives exhibited antitopoisomerase IIα activity at 100 μM and were cytotoxic against MCF-7 and T47-D breast tumor cells, particularly against the more aggressive T47-D lineage. No hemolytic activity was observed in human erythrocytes. In vivo assays in zebrafish embryos showed no toxicological or cardiotoxic effects. However, all compounds altered superoxide dismutase (SOD) and catalase (CAT) enzymatic activity, requiring further studies on reactive oxygen species (ROS) generation to assess potential adverse effects. Furthermore, significant results were observed in the physicochemical and pharmacokinetic parameters of the synthesized compounds. Conclusions: The findings highlight the quinoline derivative (3b) as the most promising nitrogen heterocycle due to its antiproliferative activity and biomolecular interactions without adverse effects in zebrafish embryos, distinguishing it from clinically available agents. Full article
(This article belongs to the Special Issue Synthesis, In Silico Prediction and Antitumor Activity of Nitrogen Heterocycle-Based Drug Development)
►▼ Show Figures

Graphical abstract

21 pages, 7516 KB  
Article
In Silico Discovery of ABZI Nitrogen Heterocycle STING Agonists via 3D-QSAR, Molecular Dynamics, and AI-Based Synthesis Prediction
by Houcheng Ren, Yuhong Jin, Baipu Zhao, Xiangbing Peng, Shan Zhao and Meiting Wang
Pharmaceuticals 2026, 19(3), 387; https://doi.org/10.3390/ph19030387 - 28 Feb 2026
Viewed by 666
Abstract
Background/Objectives: The stimulator of interferon genes (STING) pathway plays a central role in innate immune signaling and represents an attractive therapeutic target for cancer immunotherapy. Amidobenzimidazole (ABZI) derivatives have emerged as promising non-nucleotide STING agonists with improved drug-like properties compared to cyclic [...] Read more.
Background/Objectives: The stimulator of interferon genes (STING) pathway plays a central role in innate immune signaling and represents an attractive therapeutic target for cancer immunotherapy. Amidobenzimidazole (ABZI) derivatives have emerged as promising non-nucleotide STING agonists with improved drug-like properties compared to cyclic dinucleotides. However, current ABZI compounds still exhibit limited oral bioavailability and cross-species potency discrepancies. In addition, potential systemic toxicity remains a concern, indicating the need for further structural optimization. Methods: In this study, a comprehensive computer-aided drug design strategy was employed to systematically investigate ABZI derivatives and identify novel STING agonists with enhanced activity and favorable pharmacokinetic profiles. A 3D quantitative structure–activity relationship (3D-QSAR) model was constructed using the Topomer CoMFA approach based on a dataset of 109 reported ABZI compounds. Guided by the contour map analysis, new chemical groups were introduced through a fragment growth method, generating a large virtual library. The library was subsequently filtered via molecular docking, molecular dynamics simulations, and MM-PBSA binding free energy calculations. Results: Among the newly designed ABZI compounds, five compounds displayed lower binding free energies than D59, with M13 and M44 showing reductions exceeding 6.7 kcal/mol. This work demonstrates the effectiveness of an integrated in silico design strategy for the discovery of novel STING agonists. Conclusions: The identified compounds represent promising candidates for subsequent experimental validation and may support the development of nitrogen heterocycle-based STING agonists for antitumor applications. Full article
(This article belongs to the Special Issue Synthesis, In Silico Prediction and Antitumor Activity of Nitrogen Heterocycle-Based Drug Development)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-2
Back to TopTop