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Special Issue "Multicomponent Reaction-Based Synthesis of Bioactive Molecules"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 June 2017)

Special Issue Editors

Guest Editor
Prof. Dr. Diego Muñoz-Torrero

Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, Av. Joan XXIII, 27-31, Barcelona E-08028, Spain
Website | E-Mail
Interests: multitarget anti-Alzheimer agents; hybrid compounds; cholinesterase inhibitors; amyloid anti-aggregating compounds; BACE-1 inhibitors; antiprotozoan compounds
Guest Editor
Prof. Dr. Rodolfo Lavilla

Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII, 27-31, Barcelona E-08028, Spain
Website | E-Mail
Interests: multicomponent reactions; heterocyclic chemistry; scaffolds for medicinal chemistry; functional fluorophores; chemical biology
Guest Editor
Prof. Dr. Christopher Hulme

Department of Pharmacology and Toxicology, and Department of Chemistry and Biochemistry, College of Pharmacy, The University of Arizona, Biological Sciences West Room 351, 1041 East Lowell Street, Tucson, Arizona 85721, USA
Website | E-Mail
Interests: multicomponent reactions; medicinal chemistry; diversity oriented synthesis; neurodegeneration

Special Issue Information

Dear Colleagues,

Multicomponent reactions (MCRs) involve the one-pot combination of three or more reactants to afford single products that feature structural elements of all the starting materials, thereby displaying a high degree of synthetic efficiency and atom economy. Because of their modular features, MCRs generate complex products, ideally in one step, amenable to a broad range of substitution patterns. This strategy represents a powerful tool for combinatorial and diversity-oriented synthesis, and hence, a compelling approach for new hit discovery and hit-to-lead optimization campaigns. As a consequence, MCRs are having a tremendous impact in drug discovery both in the pharmaceutical industry and in academia.

In this Special Issue, we intend to collect original research articles and short communications about medicinal chemistry projects where MCRs have played an important role in the synthesis of the target biologically active compounds or their advanced precursors. Review articles that address the role of known MCRs and the design of novel MCRs for drug discovery will be also welcome.

Prof. Dr. Diego Muñoz-Torrero
Prof. Dr. Rodolfo Lavilla
Prof. Dr. Christopher Hulme
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 papers will be 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 100 words) can be sent to the Editorial Office for announcement on this website.

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. Molecules 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 1800 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

  • multicomponent reactions
  • drug discovery
  • hit-to-lead optimization
  • diversity-oriented synthesis
  • structural complexity
  • exploratory power
  • iterative efficiency

Published Papers (6 papers)

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Research

Open AccessArticle Multienzyme Biosynthesis of Dihydroartemisinic Acid
Molecules 2017, 22(9), 1422; doi:10.3390/molecules22091422
Received: 13 August 2017 / Revised: 27 August 2017 / Accepted: 27 August 2017 / Published: 28 August 2017
PDF Full-text (2463 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
One-pot multienzyme biosynthesis is an attractive method for producing complex, chiral bioactive compounds. It is advantageous over step-by-step synthesis, as it simplifies the process, reduces costs and often leads to higher yield due to the synergistic effects of enzymatic reactions. In this study,
[...] Read more.
One-pot multienzyme biosynthesis is an attractive method for producing complex, chiral bioactive compounds. It is advantageous over step-by-step synthesis, as it simplifies the process, reduces costs and often leads to higher yield due to the synergistic effects of enzymatic reactions. In this study, dihydroartemisinic acid (DHAA) pathway enzymes were overexpressed in Saccharomyces cerevisiae, and whole-cell biotransformation of amorpha-4,11-diene (AD) to DHAA was demonstrated. The first oxidation step by cytochrome P450 (CYP71AV1) is the main rate-limiting step, and a series of N-terminal truncation and transcriptional tuning improved the enzymatic activity. With the co-expression of artemisinic aldehyde dehydrogenase (ALDH1), which recycles NADPH, a significant 8-fold enhancement of DHAA production was observed. Subsequently, abiotic conditions were optimized to further enhance the productivity of the whole-cell biocatalysts. Collectively, approximately 230 mg/L DHAA was produced by the multi-step whole-cell reaction, a ~50% conversion from AD. This study illustrates the feasibility of producing bioactive compounds by in vitro one-pot multienzyme reactions. Full article
(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)
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Open AccessArticle A New Approach to Synthesize of 4-Phenacylideneflavene Derivatives and to Evaluate Their Cytotoxic Effects on HepG2 Cell Line
Molecules 2017, 22(8), 1296; doi:10.3390/molecules22081296
Received: 29 June 2017 / Accepted: 2 August 2017 / Published: 9 August 2017
PDF Full-text (722 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, a convenient approach and green procedure for the synthesis of 4-phenacylideneflavenes has been developed from the reaction between 2,4-dihydroxybenzaldehyde and substituted acetophenones using boric acid as a catalyst in polyethylene glycol 400. Seven 4-phenacylideneflavenes were synthetized and their structures were
[...] Read more.
In this study, a convenient approach and green procedure for the synthesis of 4-phenacylideneflavenes has been developed from the reaction between 2,4-dihydroxybenzaldehyde and substituted acetophenones using boric acid as a catalyst in polyethylene glycol 400. Seven 4-phenacylideneflavenes were synthetized and their structures were confirmed by NMR and mass spectral analyses. Meanwhile, their possible mechanism of formation was also discussed. These products were found to have potential cytotoxic effect on HepG2 cell line with IC50 values from 12.5 to 50 µM. Full article
(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)
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Open AccessArticle An Efficient One-Pot Catalyzed Synthesis of 2,4-Disubstituted 5-Nitroimidazoles Displaying Antiparasitic and Antibacterial Activities
Molecules 2017, 22(8), 1278; doi:10.3390/molecules22081278
Received: 20 July 2017 / Accepted: 29 July 2017 / Published: 3 August 2017
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Abstract
A one-pot regioselective bis-Suzuki-Miyaura or Suzuki-Miyaura/Sonogashira reaction on 2,4-dibromo-1-methyl-5-nitro-1H-imidazole under microwave heating was developed. This method is applicable to a wide range of (hetero)arylboronic acids and terminal alkynes. Additionally, this approach provides a simple and efficient way to synthesize 2,4-disubstituted 5-nitroimidazole
[...] Read more.
A one-pot regioselective bis-Suzuki-Miyaura or Suzuki-Miyaura/Sonogashira reaction on 2,4-dibromo-1-methyl-5-nitro-1H-imidazole under microwave heating was developed. This method is applicable to a wide range of (hetero)arylboronic acids and terminal alkynes. Additionally, this approach provides a simple and efficient way to synthesize 2,4-disubstituted 5-nitroimidazole derivatives with antibacterial and antiparasitic properties. Full article
(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)
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Open AccessArticle Synthesis and Biological Evaluation of New Substituted Hantzsch Thiazole Derivatives from Environmentally Benign One-Pot Synthesis Using Silica Supported Tungstosilisic Acid as Reusable Catalyst
Molecules 2017, 22(5), 757; doi:10.3390/molecules22050757
Received: 10 March 2017 / Revised: 2 May 2017 / Accepted: 4 May 2017 / Published: 7 May 2017
Cited by 1 | PDF Full-text (930 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An efficient and green method has been developed for the synthesis of new substituted Hantzsch thiazole derivatives in 79%–90% yield, via the one-pot multi-component procedure, by the reaction of 3-(bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, thiourea and substituted benzaldehydes in the presence of silica supported tungstosilisic
[...] Read more.
An efficient and green method has been developed for the synthesis of new substituted Hantzsch thiazole derivatives in 79%–90% yield, via the one-pot multi-component procedure, by the reaction of 3-(bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, thiourea and substituted benzaldehydes in the presence of silica supported tungstosilisic acid, as a reusable catalyst, under conventional heating or under ultrasonic irradiation. The catalyst is recoverable by a simple filtration and can be reused in the subsequent reactions. Most of the thiazoles exhibited significant antibacterial activity compared toamoxicillin and ciprofloxacin as positive controls. In addition, the new compounds showed moderate to good antioxidant (DPPH) radical scavenging activity. Full article
(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)
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Open AccessArticle An Efficient One-Pot Protocol for the Synthesis of Substituted 3,4-Dihydropyrimidin-2(1H)-ones Using Metallophthalocyanines (MPcs) as Potent Heterogeneous Catalysts: Synthesis, Characterization, Aggregation and Antimicrobial Activity
Molecules 2017, 22(4), 605; doi:10.3390/molecules22040605
Received: 3 February 2017 / Revised: 15 March 2017 / Accepted: 23 March 2017 / Published: 9 April 2017
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Abstract
In this study, novel phthalonitrile 3 and their corresponding metal-free 4 and metallophthalocyanine derivatives 57 bearing 2-isopropenyl-4-methoxy-1-methylbenzene groups were synthesized and characterized. 3,4-Dihydropyrimidinones have been synthesized by a modified Biginelli-type reaction with various metallophthalocyanines 57 as catalysts. Compared to
[...] Read more.
In this study, novel phthalonitrile 3 and their corresponding metal-free 4 and metallophthalocyanine derivatives 57 bearing 2-isopropenyl-4-methoxy-1-methylbenzene groups were synthesized and characterized. 3,4-Dihydropyrimidinones have been synthesized by a modified Biginelli-type reaction with various metallophthalocyanines 57 as catalysts. Compared to the classical Biginielli reaction, the new method has the advantages of good yield and short reaction time. Among the various metallophthalocyanines studied, cobalt (II)-phthalocyanine was found to be most active for this transformation. The newly prepared compounds were characterized using elemental analyses, MS, IR, 1H/13C-NMR and UV-Vis spectroscopy. In addition; the 3,4-dihydropyrimidinones (DHPMs) 812 were investigated for antimicrobial activities and revealed good activity. The minimum inhibitory concentration (MIC) was determined by the microdilution technique in Mueller-Hinton broth. The MICs were recorded after 24 hours of incubation at 37 °C. These results are promising, showing these compounds are biologically active. Full article
(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)
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Open AccessCommunication Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products
Molecules 2017, 22(2), 254; doi:10.3390/molecules22020254
Received: 3 January 2017 / Revised: 30 January 2017 / Accepted: 3 February 2017 / Published: 8 February 2017
Cited by 1 | PDF Full-text (2134 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that
[...] Read more.
The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction—namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1) as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid. Full article
(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)
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