Special Issue "Medicinal Chemistry of Indole and Quinoline Derivatives: Trends, and Future Directions as Therapeutic Drugs"

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

Deadline for manuscript submissions: 20 March 2024 | Viewed by 1275

Special Issue Editor

School of Chemistry, Analytical and Biological Chemistry Research Facility, University College Cork, College Road, T12 K8AF Cork, Ireland
Interests: indoles; quinolines; quinones; heterocycles; kinase inhibitors; plant sterols; pharmaceutical discovery and development

Special Issue Information

Dear Colleagues,

Nitrogen-containing heterocycles have made an enormous contribution to medicinal and pharmaceutical chemistry since the identification of alkaloids such as morphine and strychnine. The prevalence and potency of nitrogen-containing natural products that incorporate indole and quinoline (with melatonin, quinine, serotonin and tryptophan as other examples) frame this success.  

The two bicyclic ring systems have provided a rich source of diversity, upon which medicinal and pharmaceutical chemistry has thrived, and multiple examples of therapeutics with real-life benefits exist. Examples on the WHO Essential Medicines List stretch from chloroquine (discovered in 1934) to ciprofloxacin, fluvastatin, indomethacin, mefloquine, ondansetron, primaquine, quinine and sumatriptan. More recently, aripiprazole, tadalafil and ziprasidone are some of the most commonly prescribed medicines and highlight the tangible impact of these heterocycles on people and the treatment of their diseases.  

Medicinal chemistry approaches to find small-molecule lead compounds with pharmacological activity continue to use natural products, synthesis and existing small-molecule drug libraries as sources. The focus of this series of papers is the use of indole and quinoline as therapeutics. 

The journal Pharmaceuticals invites both reviews and original articles which concern the use of indoles and  quinolines in the discovery and development of pharmaceuticals. The scope of the Special Issue will cover, but is not limited to: new synthetic methods in the synthesis of indoles and quinolines, medicinal chemistry and structure–activity studies of indole and quinoline derivatives, natural product discovery involving indoles and quinolines,  indole and quinoline drug repositioning, new combinations of indoles and quinolines, and indoles and quinolines beyond pharmaceutical applications. The collection of manuscripts will be published as a Special Issue of the journal.

Dr. Florence O. McCarthy
Guest Editor

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 submissions that pass pre-check are 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. Pharmaceuticals 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 2900 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.


  • indole
  • quinoline
  • heterocycle
  • pharmaceutical discovery and development

Published Papers (1 paper)

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27 pages, 4368 KiB  
Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes
Pharmaceuticals 2023, 16(9), 1222; https://doi.org/10.3390/ph16091222 - 30 Aug 2023
Cited by 1 | Viewed by 721
Novel analogs of quinoline and isoindoline containing various heterocycles, such as tetrazole, triazole, pyrazole, and pyridine, were synthesized and characterized using FT-IR, NMR, and mass spectroscopy, and their antioxidant and antidiabetic activities were investigated. The previously synthesized compound 1 was utilized in conjugation [...] Read more.
Novel analogs of quinoline and isoindoline containing various heterocycles, such as tetrazole, triazole, pyrazole, and pyridine, were synthesized and characterized using FT-IR, NMR, and mass spectroscopy, and their antioxidant and antidiabetic activities were investigated. The previously synthesized compound 1 was utilized in conjugation with ketone-bearing tetrazole and isoindoline-1,3-dione to synthesize Schiff’s bases 2 and 3. Furthermore, hydrazide 1 was treated with aryledines to provide pyrazoles 4ac. Compound 5 was obtained by treating 1 with potassium thiocyanate, which was then cyclized in a basic solution to afford triazole 6. On the other hand, pyridine derivatives 7ad and 8ad were synthesized using 2-(4-acetylphenyl)isoindoline-1,3-dione via a one-pot condensation reaction with aryl aldehydes and active methylene compounds. From the antioxidant and antidiabetic studies, compound 7d showed significant antioxidant activity with an EC50 = 0.65, 0.52, and 0.93 mM in the free radical scavenging assays (DPPH, ABTS, and superoxide anion radicals). It also displayed noteworthy inhibitory activity against both enzymes α-glycosidase (IC50: 0.07 mM) and α-amylase (0.21 mM) compared to acarbose (0.09 mM α-glycosidase and 0.25 mM for α-amylase), and higher than in the other compounds. During in silico assays, compound 7d exhibited favorable binding affinities towards both α-glycosidase (−10.9 kcal/mol) and α-amylase (−9.0 kcal/mol) compared to acarbose (−8.6 kcal/mol for α-glycosidase and −6.0 kcal/mol for α-amylase). The stability of 7d was demonstrated by molecular dynamics simulations and estimations of the binding free energy throughout the simulation session (100 ns). Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

1. Type: Original article

Title: Nature-inspired 1-phenylpyrrolo[2,1-a]isoquinoline scaffold for novel antiproliferative agents circumventing P-glycoprotein-dependent multidrug resistance

Author(s): Alisa A. Nevskaya (1), Rosa Purgatorio (2), Aryna Obidennik (1), Lada V. Anikina (3), Elena Yu. Nevskaya (1), Tatiana Borisova (1), Mauro Niso (2), Antonio Carrieri (2), Marco Catto (2), Modesto de Candia (2), Leonid G. Voskressensky (2) and Cosimo D. Altomare (1)

The Corresponding author(s): Cosimo D. Altomare

(1) Organic Chemistry Department, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., 117198 Moscow, Russia
(2) Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy
(3) Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka, Russia

Abstract: Previous studies showed that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in tumor cells and may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, we synthesized and evaluated for their in-vitro antiproliferative activity in four tumor cell lines (RD, HCT116, HeLa, A549) and ability of inhibiting P-gp-mediated MDR some fifteen diversely substituted 1-Ph-DHPIQ derivatives bearing at position 2 carboxylic derivatives (COOH, COOMe), nitriles (CN) and Mannich bases (e.g., morfolinomethyl derivatives). The results improved our understanding of the structure-activity relationships of this new class of compounds and led us to disclose a novel water-soluble Mannich base, stable at pHs 2 and 7.4 at r.t., which proved to be cytotoxic to all the tested tumor cell lines in the low micromolar range (IC50 < 20 uM) and to inhibit in-vitro the efflux pumps P-gp and MRP1 responsible for multidrug resistance, with IC50s of 0.4 and 1.8 uM, respectively.
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