Synthesis of Novel Heterocyclic Compounds and Evaluation of Their Antimicrobial Activity

A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Chemical and Molecular Sciences".

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 17864

Special Issue Editors

Department of Organic Chemistry, Pharmaceutical Faculty, Poznan University of Medical Sciences, Poznan, Poland
Interests: organic medicinal chemistry; small molecules; heterocyclic compounds; isoprenoids; drug design; synthetic processes; MAOS; drug–drug conjugates; hybrid compounds as “molecular consortia”
Special Issues, Collections and Topics in MDPI journals
Department of Organic Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland
Interests: organic synthesis; heterocyclic compounds; drug design; "green" chemistry; synthetic fragrance substances; hybrid compounds
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Every year, a few new drugs are introduced to the market, both so-called small-molecular chemical compounds and biological drugs. According to regularly reported data, including by the FDA, small-molecular compounds have for many years the newest pharmaceutical products most commonly approved for therapeutic use. In 2019, 38 new chemical entities were introduced for medicinal use in the USA, almost all of them heterocyclic compounds, of which about 2/3 were nitrogen heterocycles. A similar tendency has been observed in many other countries. The above facts indicate the huge potential of applications of heterocyclic compounds of various origins—both synthetic and natural—as medicinal substances.

Heterocyclic individuals are expected to be good candidates for antimicrobial agents against infectious diseases caused by all classes of microbes, which constitute a significant percentage of all diseases affecting humanity. Potential epidemics are difficult to control, often with tragic consequences.

Therefore, the use of heterocyclic compounds, both those of completely new structures and so-called repositioned entities, to combat microbial infections of various types seems to be one of the key research directions of new small-molecule chemical drugs.

This Special Issue is dedicated to presentation of results of latest research on different kinds of heterocyclic compounds, their modern and rational synthesis, general progress, and trends in heterocyclic chemistry. We would like to kindly invite researchers from all over the world to submit their original results or reviews featuring recent developments in the area of heterocyclic derivatives use to fight malicious pathogenic microbes.

Prof. Dr. Lucjusz Zaprutko
Dr. Anna Pawelczyk
Guest Editors

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Keywords

  • organic chemistry
  • heterocyclic chemistry
  • synthetic methods
  • heterocyclic natural products
  • heterocyclic hybrids
  • heterocyclic scaffolds
  • drug design
  • antimicrobial activity
  • biological activity

Published Papers (8 papers)

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Editorial

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3 pages, 189 KiB  
Editorial
Special Issue on Synthesis of Novel Heterocyclic Compounds and Evaluation of Their Antimicrobial Activity
Appl. Sci. 2023, 13(21), 11755; https://doi.org/10.3390/app132111755 - 27 Oct 2023
Viewed by 582
Abstract
Since their discovery or, to be exact, their definition, the chemistry of heterocyclic compounds has rapidly developed, and the range of their application has grown wider [...] Full article

Research

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15 pages, 1086 KiB  
Article
In Silico and In Vitro Assessment of Antimicrobial and Antibiofilm Activity of Some 1,3-Oxazole-Based Compounds and Their Isosteric Analogues
Appl. Sci. 2022, 12(11), 5571; https://doi.org/10.3390/app12115571 - 30 May 2022
Cited by 4 | Viewed by 1525
Abstract
In this paper, we report on the antimicrobial activity assessment of 49 compounds previously synthesized as derivatives of alanine or phenylalanine that incorporate a 4-(4-X-phenylsulfonyl)phenyl fragment (X = H, Cl, or Br), namely 21 acyclic compounds (6 × N-acyl-α-amino acids, 1 × [...] Read more.
In this paper, we report on the antimicrobial activity assessment of 49 compounds previously synthesized as derivatives of alanine or phenylalanine that incorporate a 4-(4-X-phenylsulfonyl)phenyl fragment (X = H, Cl, or Br), namely 21 acyclic compounds (6 × N-acyl-α-amino acids, 1 × N-acyl-α-amino acid ester, and 14 × N-acyl-α-amino ketones) and 28 pentatomic heterocycles from the oxazole-based compound class (6 × 4H-1,3-oxazol-5-ones, 16 × 5-aryl-1,3-oxazoles, and 6 × ethyl 1,3-oxazol-5-yl carbonates). Both in silico and in vitro qualitative and quantitative assays were used to investigate the antimicrobial potential of these derivatives against planktonic and biofilm-embedded microbial strains. Some of the tested compounds showed promising antimicrobial and antibiofilm activity depending on their chemical scaffold and lipophilic character. Full article
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20 pages, 5893 KiB  
Article
Antimicrobial Activity and In Silico Molecular Docking Studies of Pentacyclic Spiro[oxindole-2,3′-pyrrolidines] Tethered with Succinimide Scaffolds
Appl. Sci. 2022, 12(1), 360; https://doi.org/10.3390/app12010360 - 30 Dec 2021
Cited by 9 | Viewed by 1814
Abstract
Three-component cascade reactions of (E)-3-arylidene-1-methyl-pyrrolidine-2,5-diones, L-valine and various isatin derivatives are described. A series of 17 spiropyrrolidine derivatives with wide structural complexity and diversity have been thus obtained in moderate to excellent yields under mild reaction conditions. The structure and [...] Read more.
Three-component cascade reactions of (E)-3-arylidene-1-methyl-pyrrolidine-2,5-diones, L-valine and various isatin derivatives are described. A series of 17 spiropyrrolidine derivatives with wide structural complexity and diversity have been thus obtained in moderate to excellent yields under mild reaction conditions. The structure and stereochemistry of these N-heterocyclic cycloadducts has been established by spectroscopic techniques and unambiguously confirmed by a single-crystal X-ray diffraction analysis performed on one derivative. UV-visible spectra have been recorded for all new compounds. Furthermore, the synthesized N-heterocyclic compounds have been screened for their in vitro antibacterial and antifungal activities. Several derivatives exhibited moderate to good activities, comparable to those of the known standard drugs Amphotericin B and Tetracycline. Structural activity relationships (SARs) and molecular docking of the most promising derivatives into the binding sites of glucosamine 6-phosphate synthase (GlcN6P) and methionyl-trna-synthetase (1PFV) were also established. Furthermore, pharmacokinetic studies indicate that the heterocycles exhibit acceptable predictive ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties and good drug ability. Full article
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15 pages, 8859 KiB  
Article
New Water-Soluble Condensed Heterocyclic Compounds with Antimicrobial Activity Based on Annulation Reactions of 8-Quinolinesulfenyl Halides with Natural Products and Alkenes
Appl. Sci. 2021, 11(18), 8532; https://doi.org/10.3390/app11188532 - 14 Sep 2021
Cited by 1 | Viewed by 1660
Abstract
The annulation reactions of 8-quinolinesulfenyl halides with natural products and alkenes affording new water-soluble [1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives in high or quantitative yields are developed in this study. The reactions with styrene derivatives and terminal alkenes including allyl arenes proceed in a regioselective [...] Read more.
The annulation reactions of 8-quinolinesulfenyl halides with natural products and alkenes affording new water-soluble [1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives in high or quantitative yields are developed in this study. The reactions with styrene derivatives and terminal alkenes including allyl arenes proceed in a regioselective manner but with the opposite regiochemistry. The reactions with terminal alkenes including allyl arenes occur in an anti-Markovnikov fashion (regarding addition of the 8-quinolinesulfenyl electrophile to the double bond) to give 2-organyl-2H,3H-[1,4]thiazino[2,3,4-ij]quinolin-4-ium halides, while the reactions with styrene derivatives proceed in a Markovnikov fashion, leading to 3-substituted condensed heterocyclic compounds. In general, styrene derivatives demonstrate higher reactivity in the annulation reactions compared to the terminal alkenes. Antimicrobial activity of novel water-soluble compounds against Enterococcus durans, Bacillus subtilis and Escherichia coli are evaluated. The compounds with high antimicrobial activity are found. The annulation products of the reactions of 8-quinolinesulfenyl halides with 1H-indene, eugenol, methyl eugenol and 1-heptene, are superior in their activity compared to the antibiotic gentamicin. Full article
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12 pages, 2985 KiB  
Article
Synthesis and Physicochemical Properties of [(1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy]-thiophen-5-yl-substituted Tetrapyrazinoporphyrazine with Magnesium(II) Ion
Appl. Sci. 2021, 11(6), 2576; https://doi.org/10.3390/app11062576 - 13 Mar 2021
Cited by 1 | Viewed by 1709
Abstract
Tetrapyrazinoporphyrazine with peripheral menthol-thiophenyl substituents was synthesized using Linstead conditions and purified by flash column chromatography. The optimized synthetic and purification procedures allowed us to obtain a new macrocycle with 36% yield. Tetrapyrazinoporphyrazine derivative was characterized by UV–Vis and NMR spectroscopy, as well [...] Read more.
Tetrapyrazinoporphyrazine with peripheral menthol-thiophenyl substituents was synthesized using Linstead conditions and purified by flash column chromatography. The optimized synthetic and purification procedures allowed us to obtain a new macrocycle with 36% yield. Tetrapyrazinoporphyrazine derivative was characterized by UV–Vis and NMR spectroscopy, as well as MS spectrometry. Complex NMR studies using 1D and 2D NMR techniques allowed the analysis of the bulky menthol-thiophenyl substituted periphery of the new macrocycle. Further, photochemical stability and singlet oxygen quantum yield were determined by indirect method with diphenylisobenzofuran. The new tetrapyrazinoporphyrazine revealed low generation of singlet oxygen with a quantum yield of singlet oxygen formation at 2.3% in dimethylformamide. In turn, the macrocycle under irradiation with visible light presented very high stability with quantum yield for photostability of 9.59 × 10−6 in dimethylformamide, which figures significantly exceed the border for its classification as a stable porphyrinoid (10−4–10−5). Full article
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12 pages, 2681 KiB  
Article
Novel Derivatives of 4-Methyl-1,2,3-Thiadiazole-5-Carboxylic Acid Hydrazide: Synthesis, Lipophilicity, and In Vitro Antimicrobial Activity Screening
Appl. Sci. 2021, 11(3), 1180; https://doi.org/10.3390/app11031180 - 27 Jan 2021
Cited by 12 | Viewed by 2279
Abstract
Bacterial infections, especially those caused by strains resistant to commonly used antibiotics and chemotherapeutics, are still a current threat to public health. Therefore, the search for new molecules with potential antimicrobial activity is an important research goal. In this article, we present the [...] Read more.
Bacterial infections, especially those caused by strains resistant to commonly used antibiotics and chemotherapeutics, are still a current threat to public health. Therefore, the search for new molecules with potential antimicrobial activity is an important research goal. In this article, we present the synthesis and evaluation of the in vitro antimicrobial activity of a series of 15 new derivatives of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid. The potential antimicrobial effect of the new compounds was observed mainly against Gram-positive bacteria. Compound 15, with the 5-nitro-2-furoyl moiety, showed the highest bioactivity: minimum inhibitory concentration (MIC) = 1.95–15.62 µg/mL and minimum bactericidal concentration (MBC)/MIC = 1–4 µg/mL. Full article
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Review

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18 pages, 14901 KiB  
Review
A Review on the Advancements in the Field of Metal Complexes with Schiff Bases as Antiproliferative Agents
Appl. Sci. 2021, 11(13), 6027; https://doi.org/10.3390/app11136027 - 29 Jun 2021
Cited by 58 | Viewed by 4815
Abstract
Metal complexes play an essential role in pharmaceutical sciences for their multiple and important activities. Schiff bases are versatile pharmacophores able to form chelating complexes with several metals in different oxidation states. Complexes with Schiff bases are widely described in the literature for [...] Read more.
Metal complexes play an essential role in pharmaceutical sciences for their multiple and important activities. Schiff bases are versatile pharmacophores able to form chelating complexes with several metals in different oxidation states. Complexes with Schiff bases are widely described in the literature for their multiple actions and numerous advantages, such as low cost and easy synthesis. They show multiple biological activities, including antimicrobial, antioxidant, antimalarial, antinflammatory and antitumor. Schiff bases may also form complexes with lanthanides and actinides acting as catalysts (e.g., in various synthetic processes) and antitumor agents. This review intends to extend on our previous paper regarding Schiff bases as antitumorals, highlighting the importance, in the field of the anticancer agents, of these tools as ligands of metal complexes. Full article

Other

27 pages, 1749 KiB  
Concept Paper
Antimicrobial and Odour Qualities of Alkylpyrazines Occurring in Chocolate and Cocoa Products
Appl. Sci. 2022, 12(22), 11361; https://doi.org/10.3390/app122211361 - 09 Nov 2022
Cited by 4 | Viewed by 1691
Abstract
A total of 40 pyrazine compounds of cocoa and chocolate were discovered through a literature analysis. Data on the alkylpyrazines’ antibacterial properties were gathered. It was discovered that 12 substances were effective against bacteria, fungus and oomycetes. Following calculations using PASS and AntiBac-Pred, [...] Read more.
A total of 40 pyrazine compounds of cocoa and chocolate were discovered through a literature analysis. Data on the alkylpyrazines’ antibacterial properties were gathered. It was discovered that 12 substances were effective against bacteria, fungus and oomycetes. Following calculations using PASS and AntiBac-Pred, 15 substances were identified as potentially having the ability to inhibit the growth of the Picornavirus, Yersinia pestis, Resistant Mycobacterium tuberculosis, Mycobacterium bovis BCG (Bacillus Calmette-Guerin), Micrococcus luteus and Corynebacterium jeikeium. The study of odour qualities led to the identification of the most potent odourants among alkylpyrazines as well as the aroma composition of cocoa and chocolate. Pyrazines have been given GRAS (generally recognized as safe) status by the Flavor and Extract Manufacturers Association (FEMA) for use as flavouring additives in food, demonstrating that this class of chemicals is a secure substitute for managing and combating microbial contamination, which also provides beneficial odour properties to the recipient. A statistical evaluation of the correlation between the odour threshold and the probability of antibacterial activity was performed. A more in-depth investigation of the antimicrobial and olfactory activities of alkylpyrazines is required in the future. Full article
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