Synthetic Chemistry in Drug Discovery: Novel Compounds for Antimicrobial and Antioxidant Applications

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: 16 October 2025 | Viewed by 330

Special Issue Editor


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Guest Editor
Department of Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy
Interests: organic chemistry; pharmaciutical chemistry

Special Issue Information

Dear Colleagues,

This Special Issue focuses on recent advances in synthetic chemistry targeting the discovery of novel antimicrobial, antiproliferative, and antioxidant agents. The emergence of drug-resistant pathogens and oxidative stress-related disorders highlights the urgent need for innovative therapeutic strategies. Synthetic approaches enable the rational design and structural optimization of small molecules with improved efficacy, selectivity, and pharmacokinetic profiles. This Special Issue invites original research and review articles on the synthesis, characterization, and biological evaluation of active compounds with antimicrobial, antiproliferative, and antioxidant properties. Contributions exploring structure–activity relationships, natural product-inspired scaffolds, hybrid molecules, and mechanisms of action are encouraged. Studies employing in vitro, in vivo, or in silico methods to validate bioactivity are welcome. The goal is to provide a multidisciplinary platform integrating synthetic methodologies with pharmacological insights to accelerate the development of effective therapeutic candidates.

Dr. Hawraz Ibrahim M. Amin
Guest Editor

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Keywords

  • synthetic chemistry
  • drug discovery
  • essential oils
  • antimicrobial activity
  • antiproliferative agents
  • antioxidant properties
  • bioactive molecules
  • structure–activity relationship
  • natural product derivatives
  • medicinal chemistry
  • chemical synthesis
  • pharmacological evaluation

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Published Papers (1 paper)

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Research

18 pages, 2274 KB  
Article
Isoniazid-Derived Hydrazones Featuring Piperazine/Piperidine Rings: Design, Synthesis, and Investigation of Antitubercular Activity
by Esma Özcan, Siva Krishna Vagolu, Rasoul Tamhaev, Christian Lherbet, Lionel Mourey, Tone Tønjum, Miyase Gözde Gündüz and Şengül Dilem Doğan
Biomolecules 2025, 15(9), 1305; https://doi.org/10.3390/biom15091305 - 11 Sep 2025
Viewed by 178
Abstract
Isoniazid (isonicotinic acid hydrazide, INH) is a key drug used to treat tuberculosis (TB), which continues to be the world’s most lethal infectious disease. Nevertheless, the efficacy of INH has diminished because of the emergence of Mycobacterium tuberculosis (Mtb) strains that [...] Read more.
Isoniazid (isonicotinic acid hydrazide, INH) is a key drug used to treat tuberculosis (TB), which continues to be the world’s most lethal infectious disease. Nevertheless, the efficacy of INH has diminished because of the emergence of Mycobacterium tuberculosis (Mtb) strains that are resistant to INH. Our goal in this study was to modify INH to reduce this significant resistance chemically. We synthesized INH-based hydrazones (IP1IP13) through the reaction of INH with in-house obtained benzaldehydes carrying a piperidine or piperazine ring in refluxing ethanol. Upon confirmation of their proposed structures by various spectral techniques, IP1IP13 were evaluated for their antimycobacterial capacity against Mtb H37Rv strain and INH-resistant clinical isolates with katG and inhA mutations using the Microplate Alamar Blue Assay (MABA). The compounds were additionally tested for their cytotoxicity. The obtained data indicated that the compounds with moderately increased lipophilicity compared to INH (IP7IP13) were promising antitubercular drug candidates, exhibiting drug-like properties and negligible cytotoxicity. Out of these, IP11 (N′-(4-(4-cyclohexylpiperazin-1-yl)benzylidene)isonicotinohydrazide) emerged as the most promising derivative, demonstrating the lowest MIC values against all Mtb strains tested. Subsequently, the target molecules were evaluated for their capacity to inhibit enoyl acyl carrier protein reductase (InhA), the main target enzyme of INH. Except for IP11 demonstrating 81% InhA inhibition at a concentration of 50 μM, direct InhA inhibition was shown not to be the primary mechanism responsible for the antitubercular activity of the compounds. The binding mechanism of IP11 to InhA was analyzed through molecular docking and molecular dynamics simulations. Altogether, our research identified a novel approach to modify INH to address the challenges posed by the rising prevalence of drug-resistant Mtb strains. Full article
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