Molecules

Research

Jump to: Review

11 pages, 3879 KiB

Open AccessArticle

A Two-Step Synthesis of Unprotected 3-Aminoindoles via Post Functionalization with Nitrostyrene

by Nicolai A. Aksenov, Nikolai A. Arutiunov, Igor A. Kurenkov, Vladimir V. Malyuga, Dmitrii A. Aksenov, Daria S. Momotova, Anna M. Zatsepilina, Elizaveta A. Chukanova, Alexander V. Leontiev and Alexander V. Aksenov

Molecules 2023, 28(9), 3657; https://doi.org/10.3390/molecules28093657 - 23 Apr 2023

Viewed by 1425

Abstract

A novel, low-cost method for the preparation of not easily accessible free 3-aminoindoles has been developed. This approach is based on a well-established reaction between indoles and nitrostyrene in the presence of phosphorous acid, which results in the formation of 4′-phenyl-4′H-spiro[indole-3,5′-isoxazoles]. The latter [...] Read more.

A novel, low-cost method for the preparation of not easily accessible free 3-aminoindoles has been developed. This approach is based on a well-established reaction between indoles and nitrostyrene in the presence of phosphorous acid, which results in the formation of 4′-phenyl-4′H-spiro[indole-3,5′-isoxazoles]. The latter could be transformed to corresponding aminated indoles by reaction with hydrazine hydrate in good or excellent yields upon microwave-assisted heating. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds)

► Show Figures

Scheme 1

13 pages, 1546 KiB

Open AccessArticle

Synthesis and Cytotoxic Activity of the Derivatives of N-(Purin-6-yl)aminopolymethylene Carboxylic Acids and Related Compounds

by Victor P. Krasnov, Olga A. Vozdvizhenskaya, Maria A. Baryshnikova, Alexandra G. Pershina, Vera V. Musiyak, Tatyana V. Matveeva, Kseniya V. Nevskaya, Olga Y. Brikunova, Dmitry A. Gruzdev and Galina L. Levit

Molecules 2023, 28(4), 1853; https://doi.org/10.3390/molecules28041853 - 15 Feb 2023

Cited by 1 | Viewed by 1460

Abstract

Testing a number of N-[omega-(purin-6-yl)aminoalkanoyl] derivatives of 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine in a panel of nine tumor cell lines has shown that the studied compounds exhibit high cytotoxic activity, especially against 4T1 murine mammary carcinoma, COLO201 human colorectal adenocarcinoma, SNU-1 human gastric carcinoma, [...] Read more.

Testing a number of N-[omega-(purin-6-yl)aminoalkanoyl] derivatives of 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine in a panel of nine tumor cell lines has shown that the studied compounds exhibit high cytotoxic activity, especially against 4T1 murine mammary carcinoma, COLO201 human colorectal adenocarcinoma, SNU-1 human gastric carcinoma, and HepG2 human hepatocellular carcinoma cells. Synthesis and study of structural analogs of these compounds made it possible to find that the presence of both a difluorobenzoxazine fragment and a purine residue bound via a linker of a certain length is crucial for the manifestation of the cytotoxic activity of this group of compounds. The study of the effect of the most promising compound on the cell cycle of the human tumor cell lines, the most sensitive and least sensitive to cytotoxic action (MDA-MB-231 breast adenocarcinoma and COLO201 colorectal adenocarcinoma, respectively), allows us to conclude that this compound is an inhibitor of DNA biosynthesis. The found group of purine conjugates may be of interest in the design of new antitumor agents. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds)

► Show Figures

Graphical abstract

9 pages, 2713 KiB

Open AccessCommunication

Photochromic and Luminescent Properties of a Salt of a Hybrid Molecule Based on C₆₀ Fullerene and Spiropyran—A Promising Approach to the Creation of Anticancer Drugs

by Artur A. Khuzin, Dim I. Galimov and Liliya L. Khuzina

Molecules 2023, 28(3), 1107; https://doi.org/10.3390/molecules28031107 - 22 Jan 2023

Viewed by 1424

Abstract

For the first time a pyrrolidinofullerene salt containing a spiropyran group and an ammonium group, capable of reversibly reacting to UV radiation, has been synthesized. Photoinduced reactions of the synthesized compounds were studied using absorption and luminescence spectroscopies, spectral and kinetic characteristics were [...] Read more.

For the first time a pyrrolidinofullerene salt containing a spiropyran group and an ammonium group, capable of reversibly reacting to UV radiation, has been synthesized. Photoinduced reactions of the synthesized compounds were studied using absorption and luminescence spectroscopies, spectral and kinetic characteristics were measured. The hybrid molecule was found to exhibit intrinsic fluorescence even in the spirocyclic form. The C₆₀ derivative showed a higher stability and better spectral and luminescent properties than the precursor. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds)

► Show Figures

Figure 1

26 pages, 3081 KiB

Open AccessArticle

Synthesis of 4-Aminopyrazol-5-ols as Edaravone Analogs and Their Antioxidant Activity

by Yanina V. Burgart, Galina F. Makhaeva, Olga P. Krasnykh, Sophia S. Borisevich, Natalia A. Agafonova, Nadezhda V. Kovaleva, Natalia P. Boltneva, Elena V. Rudakova, Evgeny V. Shchegolkov, Galina A. Triandafilova, Denis A. Gazizov, Olga G. Serebryakova, Maria V. Ulitko, Sergey L. Khursan, Victor I. Saloutin and Rudy J. Richardson

Molecules 2022, 27(22), 7722; https://doi.org/10.3390/molecules27227722 - 09 Nov 2022

Cited by 4 | Viewed by 1601

Abstract

One of the powerful antioxidants used clinically is Edaravone (EDA). We synthesized a series of new EDA analogs, 4-aminopyrazol-5-ol hydrochlorides, including polyfluoroalkyl derivatives, via the reduction of 4-hydroxyiminopyrazol-5-ones. The primary antioxidant activity of the compounds in comparison with EDA was investigated in vitro [...] Read more.

One of the powerful antioxidants used clinically is Edaravone (EDA). We synthesized a series of new EDA analogs, 4-aminopyrazol-5-ol hydrochlorides, including polyfluoroalkyl derivatives, via the reduction of 4-hydroxyiminopyrazol-5-ones. The primary antioxidant activity of the compounds in comparison with EDA was investigated in vitro using ABTS, FRAP, and ORAC tests. In all tests, 4-Amino-3-pyrazol-5-ols were effective. The lead compound, 4-amino-3-methyl-1-phenylpyrazol-5-ol hydrochloride (APH), showed the following activities: ABTS, 0.93 TEAC; FRAP, 0.98 TE; and ORAC, 4.39 TE. APH and its NH-analog were not cytotoxic against cultured normal human fibroblasts even at 100 μM, in contrast to EDA. According to QM calculations, 4-aminopyrazolols were characterized by lower gaps, IP, and η compared to 4-hydroxyiminopyrazol-5-ones, consistent with their higher antioxidant activities in ABTS and FRAP tests, realized by the SET mechanism. The radical-scavenging action evaluated in the ORAC test occurred by the HAT mechanism through OH bond breaking in all compounds, directly dependent on the dissociation energy of the OH bond. All the studied compounds demonstrated the absence of anticholinesterase activity and moderate inhibition of CES by some 4-aminopyrazolols. Thus, the lead compound APH was found to be a good antioxidant with the potential to be developed as a novel therapeutic drug candidate in the treatment of diseases associated with oxidative stress. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds)

► Show Figures

Graphical abstract

12 pages, 2133 KiB

Open AccessArticle

Novel Complexes of 3-[3-(1H-Imidazol-1-yl)propyl]-3,7-diaza-bispidines and β-Cyclodextrin as Coatings to Protect and Stimulate Sprouting Wheat Seeds

by Altynay B. Kaldybayeva, Valentina K. Yu, Aigul E. Malmakova, Tamara Li, Assel Yu. Ten, Tulegen M. Seilkhanov, Kaldybay D. Praliyev and Kenneth D. Berlin

Molecules 2022, 27(21), 7406; https://doi.org/10.3390/molecules27217406 - 01 Nov 2022

Cited by 1 | Viewed by 1510

Abstract

We report the syntheses and characterization of novel 3,7-bicycl[3.3.1]bispidines possessing an imidazolpropyl group attached to N-3, and at N-7 a Boc group, as well as a benzoylated-oximated group at C-9. These compounds were complexed with β-cyclodextrin [β-CD] and evaluated as seed protectors of [...] Read more.

We report the syntheses and characterization of novel 3,7-bicycl[3.3.1]bispidines possessing an imidazolpropyl group attached to N-3, and at N-7 a Boc group, as well as a benzoylated-oximated group at C-9. These compounds were complexed with β-cyclodextrin [β-CD] and evaluated as seed protectors of selected wheat seedlings. Using strong acid, condensations of N-substituted piperidones with the appropriate imidazolpropyl groups at N-3 and N-7 led to bispidinones 6 and 7. These intermediates were reduced to the corresponding 3,7-diazabicyclo[3.3.1]nonane targets. The oxime at C-9 was benzoylated to yield 13. Heating these 3,7-diazabicyclo[3.3.1]nonanes in ethanol with β-CD generated the complexes required. We investigated the ability of such complexes as coatings on seedlings to protect and stimulate growth of three varieties of wheat, namely Kazakhstanskaya-10, Severyanka, and Miras. The complex of 3-[3-(1H-imidazol-1-yl)propyl]-7-(3-methoxypropyl)-3,7-diazabicyclo[3.3.1]nonane (2) promoted growth in the root systems of all three wheat varieties by more than 30% in Kazakhstanskaya-10, 30% in Severyanka and 8.5% in Miras. A complex of 3-Boc-7-[3-(1H-imidazol-1-yl)propyl]-3,7-diazabicyclo[3.3.1]nonane (9) increased both shoot and root length in only the Severyanka variety. The complex of 3-(3-butoxypropyl)-7-[3-(1H-imidazol-1-yl)propyl]-3,7-diazabicyclo[3.3.1]nonane (11) stimulated both shoot growth (0.8%, 12.3%, 13.5%) and root growth (12.3%, 9.4%, 21.7%) in all three varieties of wheat, respectively. The nature of substituents on the bispidine affect the activity. Solid complexes (1:1) were generated as powders which melted above 240 °C (dec) and were characterized via elemental analyses as 1:1 complexes. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds)

► Show Figures

Figure 1

19 pages, 1327 KiB

Open AccessArticle

Synthesis and Biological Activity of N-acyl Anabasine and Cytisine Derivatives with Adamantane, Pyridine and 1,2-Azole Fragments

by Gulim K. Mukusheva, Aigerym R. Zhasymbekova, Zharkyn Zh. Zhumagalieva, Roza B. Seidakhmetova, Oralgazy A. Nurkenov, Ekaterina A. Akishina, Sergey K. Petkevich, Evgenij A. Dikusar and Vladimir I. Potkin

Molecules 2022, 27(21), 7387; https://doi.org/10.3390/molecules27217387 - 31 Oct 2022

Cited by 1 | Viewed by 1717

Abstract

A series of N-acyl derivatives of anabasine and cytisine were prepared, to discover novel, natural product-based medicinal agents. All synthesized compounds were tested for antimicrobial, antifungal, antiviral and analgesic activity. The most pronounced antibacterial activity was shown by the compounds with isoxazole [...] Read more.

A series of N-acyl derivatives of anabasine and cytisine were prepared, to discover novel, natural product-based medicinal agents. All synthesized compounds were tested for antimicrobial, antifungal, antiviral and analgesic activity. The most pronounced antibacterial activity was shown by the compounds with isoxazole fragments, while the adamantane derivatives showed the greatest antiviral effect. It was found that the majority of anabasine derivatives showed significant analgesic activity, reducing the pain response of animals to the irritating effect of acetic acid. The presence of a high level of antimicrobial and antiviral activity in newly synthesized compounds makes it possible to consider them promising for further study of their pharmacological properties. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds)

► Show Figures

Figure 1

18 pages, 2720 KiB

Open AccessArticle

Synthesis and Biological Activity of Unsymmetrical Monoterpenylhetaryl Disulfides

by Denis V. Sudarikov, Yulia V. Gyrdymova, Alexander V. Borisov, Julia M. Lukiyanova, Roman V. Rumyantcev, Oksana G. Shevchenko, Diana R. Baidamshina, Nargiza D. Zakarova, Airat R. Kayumov, Ekaterina O. Sinegubova, Alexandrina S. Volobueva, Vladimir V. Zarubaev and Svetlana A. Rubtsova

Molecules 2022, 27(16), 5101; https://doi.org/10.3390/molecules27165101 - 10 Aug 2022

Cited by 6 | Viewed by 1501

Abstract

New unsymmetrical monoterpenylhetaryl disulfides based on heterocyclic disulfides and monoterpene thiols were synthesized for the first time in 48–88% yields. Hydrolysis of disulfides with fragments of methyl esters of 2-mercaptonicotinic acid was carried out in 73–95% yields. The obtained compounds were evaluated for [...] Read more.

New unsymmetrical monoterpenylhetaryl disulfides based on heterocyclic disulfides and monoterpene thiols were synthesized for the first time in 48–88% yields. Hydrolysis of disulfides with fragments of methyl esters of 2-mercaptonicotinic acid was carried out in 73–95% yields. The obtained compounds were evaluated for antioxidant, antibacterial, antifungal activity, cytotoxicity and mutagenicity. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds)

► Show Figures

Figure 1

11 pages, 864 KiB

Open AccessArticle

Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine and Evaluation of Their Antiviral Activity

by Victor P. Krasnov, Vera V. Musiyak, Galina L. Levit, Dmitry A. Gruzdev, Valeriya L. Andronova, Georgii A. Galegov, Iana R. Orshanskaya, Ekaterina O. Sinegubova, Vladimir V. Zarubaev and Valery N. Charushin

Molecules 2022, 27(13), 4236; https://doi.org/10.3390/molecules27134236 - 30 Jun 2022

Cited by 5 | Viewed by 1617

Abstract

A series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine and its (S)-enantiomer attached via a 6-aminohexanoyl fragment were synthesized by the reaction of nucleophilic substitution of chlorine in various chloropyrimidines. The structures of the synthesized compounds were [...] Read more.

A series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine and its (S)-enantiomer attached via a 6-aminohexanoyl fragment were synthesized by the reaction of nucleophilic substitution of chlorine in various chloropyrimidines. The structures of the synthesized compounds were confirmed by ¹H, ¹⁹F, and ¹³C NMR spectral data. Enantiomeric purity of optically active derivatives was confirmed by chiral HPLC. Antiviral evaluation of the synthesized compounds has shown that the replacement of purine with a pyrimidine fragment leads to a decrease in the anti-herpesvirus activity compared to the lead compound, purine conjugate. The studied compounds did not exhibit significant activity against influenza A (H1N1) virus. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds)

► Show Figures

Graphical abstract

23 pages, 2665 KiB

Open AccessArticle

Antioxidant Activity and Cytotoxicity of Aromatic Oligosulfides

by Victoria Osipova, Yulia Gracheva, Maria Polovinkina, Daria Burmistrova and Nadezhda Berberova

Molecules 2022, 27(12), 3961; https://doi.org/10.3390/molecules27123961 - 20 Jun 2022

Cited by 8 | Viewed by 2082

Abstract

Natural or synthetic antioxidants with biomimetic fragments protect the functional and structural integrity of biological molecules at a minimum concentration, and may be used as potential chemotherapeutic agents. This paper is devoted to in silico and in vitro evaluation of the antioxidant and [...] Read more.

Natural or synthetic antioxidants with biomimetic fragments protect the functional and structural integrity of biological molecules at a minimum concentration, and may be used as potential chemotherapeutic agents. This paper is devoted to in silico and in vitro evaluation of the antioxidant and cytotoxic properties of synthetic analogues of natural compounds—aromatic oligosulfides. The antiradical and SOD-protective activity of oligosulfides was demonstrated in the reaction with O₂^–• generated in enzymatic and non-enzymatic systems. It was found that phenol-containing disulfides significantly reduced the accumulation level of hydroperoxides and secondary carbonyl thiobarbituric acid reactive substances, which are primary products of oleic acid peroxidation. The antioxidant efficiency of bis(3,5-di-tert-butyl-4-hydroxyphenyl) disulfide increased over time due to the synergistic action of the 2,6-di-tert-butylphenol fragment and the disulfide linker. The highest cytotoxicity on the A-549 and HCT-116 cell lines was found for bis(3,4-dimethoxyphenyl) disulfide. Significant induction of apoptosis in HCT-116 cells in the presence of bis(3,4-dimethoxyphenyl) disulfide indicates the prospect of its use as an antitumor agent. The significant and moderate dependences revealed between various types of activities of the studied aromatic oligosulfides can be used in the development of a strategy for the synthesis and study of target-oriented compounds with predictable biological activity. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds)

► Show Figures

Figure 1

22 pages, 2426 KiB

Open AccessArticle

Synthesis and Antioxidant Activity of New Catechol Thioethers with the Methylene Linker

by Ivan V. Smolyaninov, Daria A. Burmistrova, Maxim V. Arsenyev, Maria A. Polovinkina, Nadezhda P. Pomortseva, Georgy K. Fukin, Andrey I. Poddel’sky and Nadezhda T. Berberova

Molecules 2022, 27(10), 3169; https://doi.org/10.3390/molecules27103169 - 16 May 2022

Cited by 12 | Viewed by 2191

Abstract

Novel catechol thio-ethers with different heterocyclic substituents at sulfur atom were prepared by reacting 3,5-di-tert-butyl-6-methoxymethylcatechol with functionalized thiols under acidic conditions. A common feature of compounds is a methylene bridge between the catechol ring and thioether group. Two catechols with the [...] Read more.

Novel catechol thio-ethers with different heterocyclic substituents at sulfur atom were prepared by reacting 3,5-di-tert-butyl-6-methoxymethylcatechol with functionalized thiols under acidic conditions. A common feature of compounds is a methylene bridge between the catechol ring and thioether group. Two catechols with the thio-ether group, bound directly to the catechol ring, were also considered to assess the effect of the methylene linker on the antioxidant properties. The crystal structures of thio-ethers with benzo-thiazole moieties were established by single-crystal X-ray analysis. The radical scavenging and antioxidant activities were determined using 2,2′-diphenyl-1-picrylhydrazyl radical test, ABTS^∙+, CUPRAC (TEAC) assays, the reaction with superoxide radical anion generated by xanthine oxidase (NBT assay), the oxidative damage of the DNA, and the process of lipid peroxidation of rat liver (Wistar) homogenates in vitro. Most catechol-thioethers exhibit the antioxidant effect, which varies from mild to moderate depending on the model system. The dual anti/prooxidant activity characterizes compounds with adamantyl or thio-phenol substituent at the sulfur atom. Catechol thio-ethers containing heterocyclic groups (thiazole, thiazoline, benzo-thiazole, benzo-xazole) can be considered effective antioxidants with cytoprotective properties. These compounds can protect molecules of DNA and lipids from the different radical species. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds)

► Show Figures

Figure 1

Review

Jump to: Research

29 pages, 10734 KiB

Open AccessReview

Continuous-Flow Chemistry and Photochemistry for Manufacturing of Active Pharmaceutical Ingredients

by Pavlína Horáková and Kamila Kočí

Molecules 2022, 27(23), 8536; https://doi.org/10.3390/molecules27238536 - 04 Dec 2022

Cited by 4 | Viewed by 3931

Abstract

An active pharmaceutical ingredient (API) is any substance in a pharmaceutical product that is biologically active. That means the specific molecular entity is capable of achieving a defined biological effect on the target. These ingredients need to meet very strict limits; chemical and [...] Read more.

An active pharmaceutical ingredient (API) is any substance in a pharmaceutical product that is biologically active. That means the specific molecular entity is capable of achieving a defined biological effect on the target. These ingredients need to meet very strict limits; chemical and optical purity are considered to be the most important ones. A continuous-flow synthetic methodology which utilizes a continuously flowing stream of reactive fluids can be easily combined with photochemistry, which works with the chemical effects of light. These methods can be useful tools to meet these strict limits. Both of these methods are unique and powerful tools for the preparation of natural products or active pharmaceutical ingredients and their precursors with high structural complexity under mild conditions. This review shows some main directions in the field of active pharmaceutical ingredients’ preparation using continuous-flow chemistry and photochemistry with numerous examples of industry and laboratory-scale applications. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds)

► Show Figures

Scheme 1

Journal Menu

Journal Browser

Synthesis of Bioactive Compounds

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Related Special Issue

Published Papers (11 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI