Hybrid and Chimeric Heterocycles: A Promising Approach to Synthesizing Biologically Active Compounds

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

Deadline for manuscript submissions: 25 December 2025 | Viewed by 767

Special Issue Editor

Special Issue Information

Dear Colleagues,

A literature survey revealed that heterocycles are privileged core scaffolds in medicinal chemistry, playing an essential role in drug design and reported to exhibit many biological and pharmacological activities, including antimicrobial, antiviral, anthelmintic, anti-HIV, anticancer, antiallergic, diuretics, cardiotonics, antihypertensive, antiplatelet, analgesic, anxiolytic, antidepressant, hypnotic sedative, antineurodegenerative, anti-Alzheimer’s, etc.

     Despite the recent progress in obtaining new drugs with various biological activities in medicinal chemistry, there is an urgent need, in both the pharmaceutical industry and society, for new drugs with better activity, lower toxicity and enhanced properties. One of the most promising approaches used by scientists in the design of new drugs is the Multiple Targeting Drugs (MTD) approach, where a single chemical structure interacts with two or more distinct biological targets associated with a disease, resulting in new drug candidates with improved pharmacodynamic, pharmacokinetic and toxicologic properties and better patient compliance. Usually drug candidates in the Multiple Targeting Drugs approach are classified as Hybrid Drugs (HDs) or Chimeric Drugs (CDs). However, despite the advantages described above, both HDs and CDs have some drawbacks, such as decreases in target binding efficiency, side effects, toxicity, etc.

The aim of this Special Issue is to present the latest developments in biologically active compounds with a hybrid and/or chimeric heterocyclic core, with a focus on the synthesis, structure and biological activity of these compounds.

Prof. Dr. Ionel Mangalagiu
Guest Editor

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Keywords

  • hybrid heterocyclic compounds
  • chimeric heterocyclic compounds
  • multifactorial diseases
  • multiple targeting drugs
  • biological activity: antimicrobials, antiviral, anthelmintic, anti-HIV, anticancer, antiallergic, diuretics, cardiotonic, antihypertensive, antiplatelet, analgesic, anxiolytics, antidepressant, hypnotic sedative, antineurodegenerative, anti-Alzheimer’s etc.

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Published Papers (2 papers)

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Review

26 pages, 2480 KB  
Review
Promising Norlabdane-Heterocyclic Hybrids: Synthesis, Structural Characterization and Antimicrobial Activity Evaluation
by Lidia Lungu, Alexandru Ciocarlan, Ionel I. Mangalagiu and Aculina Aricu
Pharmaceuticals 2025, 18(9), 1411; https://doi.org/10.3390/ph18091411 - 19 Sep 2025
Viewed by 259
Abstract
The terpeno-heterocyclic molecular hybrids are a new and promising class of modern organic and medicinal chemistry, because their molecules exhibit high and selective biological activity, natural origins, and good biocompatibility, and, usually, they are less toxic. The reported norlabdane-heterocyclic hybrids were synthesized by [...] Read more.
The terpeno-heterocyclic molecular hybrids are a new and promising class of modern organic and medicinal chemistry, because their molecules exhibit high and selective biological activity, natural origins, and good biocompatibility, and, usually, they are less toxic. The reported norlabdane-heterocyclic hybrids were synthesized by classical and new, original, and environmentally friendly methods, which include coupling reactions of norlabdane derivatives (such as carboxylic acids, acyl chlorides, or bromides) with individual heterocyclic compounds, as well as heterocyclization reactions of certain norlabdane intermediates like hydrazides, thiosemicarbazones, or hydrazinecarbothioamides. The aforementioned norlabdanes were derived from (+)-sclareolide 2, which is readily obtained from (−)-sclareol 1, a labdane-type diterpenoid extracted from the waste biomass of Clary sage (Salvia sclarea L.) that remains after essential oil extraction. All synthesized compounds were tested against various fungal strains and bacterial species, with many exhibiting significant antifungal and antibacterial activity. These findings support the potential application of the synthesized compounds in the treatment of diseases caused by fungi and bacteria. Additionally, the use of plant-based waste materials as starting resources highlights the economic and ecological value of this approach. This review summarizes experimental data on the synthesis and biological activity of norlabdane: diazine, 1,2,4-triazole and carbazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, 1,3-thiazole, 1,3-benzothiazole and 1,3-benzimidazole hybrids performed by our research group covering the period from 2013 to the present. Full article
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28 pages, 2073 KB  
Review
Hybrid and Chimeric Heterocycles for the Inhibition of Carbonic Anhydrases
by Niccolò Paoletti, Simone Giovannuzzi and Claudiu T. Supuran
Pharmaceuticals 2025, 18(9), 1387; https://doi.org/10.3390/ph18091387 - 16 Sep 2025
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Abstract
The design of multitarget drugs is a growing strategy to address complex and multifactorial diseases, and heterocycles play a major role in this approach. This review aims to critically analyze the role of heterocyclic scaffolds in the development of human carbonic anhydrase inhibitors [...] Read more.
The design of multitarget drugs is a growing strategy to address complex and multifactorial diseases, and heterocycles play a major role in this approach. This review aims to critically analyze the role of heterocyclic scaffolds in the development of human carbonic anhydrase inhibitors (hCAIs), emphasizing their versatility as core chemotypes, linkers, and secondary pharmacophores. By examining advances from the last 10 years, we highlight how heterocycle-based designs contribute to modulating potency and selectivity toward hCAs, as well as to the creation of hybrid molecules with enhanced therapeutic profiles. Understanding these strategies is essential for guiding future drug discovery efforts targeting hCAs and related pathologies. Full article
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