MDPI - Publisher of Open Access Journals

17 pages, 6494 KB

Open AccessArticle

Synthesis of Tetrahydrocarbazole-Tethered Triazoles as Compounds Targeting Telomerase in Human Breast Cancer Cells

by Pradeep M. Uppar, Akshay Ravish, Zhang Xi, Keshav Kumar Harish, Arun M. Kumar, Lisha K. Poonacha, Toreshettahally R. Swaroop, Chaithanya Somu, Santosh L. Gaonkar, Mahendra Madegowda, Peter E. Lobie, Vijay Pandey and Basappa Basappa

Catalysts 2024, 14(10), 726; https://doi.org/10.3390/catal14100726 - 16 Oct 2024

Cited by 1 | Viewed by 1997

Abstract

Telomere shortening and the induction of senescence and/or cell death may result from inhibition of telomerase activity in cancer cells. Herein, the properties of carbazole–triazole compounds targeting telomerase in human breast cancer cells are explored. All derivatives were evaluated for loss of viability in MCF-7 breast cancer cells, with compound 5g identified as the most potent within the examined series. Green synthesis was employed using water, a reusable nano-Fe₂O₃-catalyzed reaction, and an electrochemical method for the synthesis of tetrahydrocarbazole and triazoles. The crystal data of compound 4 is also reported. Furthermore, in silico analysis predicted that compound 5g may target human telomerase. Molecular docking analysis of compound 5g towards hTERT predicted a binding affinity of −6.74 kcal/mol. In flow cytometry assays, compound 5g promoted apoptosis and cell cycle arrest in the G2-M phase. Finally, compound 5g inhibited the enzymatic activity of telomerase in human breast cancer cells. In conclusion, a green synthesized series of carbazole–triazoles that target telomerase in cancer cells is reported. Full article

(This article belongs to the Section Catalysis in Organic and Polymer Chemistry)

► Show Figures

Graphical abstract

11 pages, 2815 KB

Open AccessCommunication

Anxiolytic-Like and Antidepressant Effects of a 13H-indolo[2,3-a]thiopyrano[2,3-g]quinolizine Derivative

by Carlos E. Castillo-Espinoza, María Leonor González-Rivera, Alberto Medina-Ortiz, Juan Carlos Barragan-Galvez, Sergio Hidalgo-Figueroa, David Cruz Cruz, Martha Alicia Deveze-Alvarez, Gerardo González-García, Clarisa Villegas Gómez and Angel Josabad Alonso-Castro

Chemistry 2024, 6(3), 376-386; https://doi.org/10.3390/chemistry6030022 - 9 May 2024

Viewed by 1820

Abstract

Depressive and anxiety disorders constitute some of the most prevalent mental disorders around the world. For years, the development of new lead compounds for drug discovery in this field has been an area of great attention. Recently, a series of tetrahydrocarbazole derivatives have demonstrated important anxiolytic-like activity, associated with their structures and stereochemistry. Here, we present a study of the antidepressant effect and anxiolytic-like activity of a fused thiopyrano-piperidone-tetrahydrocarboline (compound 4). The antidepressant and anxiolytic-like effects of 4 (1–50 mg/kg p.o.) were assessed with the tail suspension test and the hole-board test, respectively. This study determined the possible mechanisms involved in the anxiolytic-like actions of 4 using inhibitors or neurotransmission and evaluated its interaction with 5HT_2A receptors using a molecular docking study. As an analog to the tetrahydrocarbazole core, the tetrahydrocarboline derivative showed anxiolytic-like activity (ED₅₀ = 13 mg/kg p.o.) in the hole-board test, with a comparable effect to the reference drug, 1.5 mg/kg clonazepam, with the possible participation of the serotonergic system. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

11 pages, 1754 KB

Open AccessArticle

Exophilone, a Tetrahydrocarbazol-1-one Analogue with Anti-Pulmonary Fibrosis Activity from the Deep-Sea Fungus Exophiala oligosperma MCCC 3A01264

by Ming-Jun Hong, Meng-Jiao Hao, Guang-Yu Zhang, Hou-Jin Li, Zong-Ze Shao, Xiu-Pian Liu, Wen-Zhe Ma, Jun Xu, Taifo Mahmud and Wen-Jian Lan

Mar. Drugs 2022, 20(7), 448; https://doi.org/10.3390/md20070448 - 9 Jul 2022

Cited by 3 | Viewed by 3080

Abstract

A new compound, exophilone (1), together with nine known compounds (2–10), were isolated from a deep-sea-derived fungus, Exophiala oligosperma. Their chemical structures, including the absolute configuration of 1, were elucidated using nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectroscopy (HRESIMS), and electronic circular dichroism (ECD) calculation. Compounds were preliminarily screened for their ability to inhibit collagen accumulation. Compounds 1, 4, and 7 showed weaker inhibition of TGF-β1-induced total collagen accumulation in compared with pirfenidone (73.14% inhibition rate). However, pirfenidone exhibited cytotoxicity (77.57% survival rate), while compounds 1, 4, and 7 showed low cytotoxicity against the HFL1 cell line. Particularly, exophilone (1) showed moderate collagen deposition inhibition effect (60.44% inhibition rate) and low toxicity in HFL1 cells (98.14% survival rate) at a concentration of 10 μM. A molecular docking study suggests that exophilone (1) binds to both TGF-β1 and its receptor through hydrogen bonding interactions. Thus, exophilone (1) was identified as a promising anti-pulmonary fibrosis agent. It has the potential to be developed as a drug candidate for pulmonary fibrosis. Full article

(This article belongs to the Special Issue Bioactive Secondary Metabolites of Marine Fungi)

► Show Figures

Figure 1

13 pages, 416 KB

Open AccessCommunication

Novel Small-Molecule Hybrid-Antibacterial Agents against S. aureus and MRSA Strains

by Robin Gehrmann, Tobias Hertlein, Elisa Hopke, Knut Ohlsen, Michael Lalk and Andreas Hilgeroth

Molecules 2022, 27(1), 61; https://doi.org/10.3390/molecules27010061 - 23 Dec 2021

Cited by 8 | Viewed by 3305

Abstract

Ongoing resistance developments against antibiotics that also affect last-resort antibiotics require novel antibacterial compounds. Strategies to discover such novel structures have been dimerization or hybridization of known antibacterial agents. We found novel antibacterial agents by dimerization of indols and hybridization with carbazoles. They were obtained in a simple one-pot reaction as bisindole tetrahydrocarbazoles. Further oxidation led to bisindole carbazoles with varied substitutions of both the indole and the carbazole scaffold. Both the tetrahydrocarbazoles and the carbazoles have been evaluated in various S. aureus strains, including MRSA strains. Those 5-cyano substituted derivatives showed best activities as determined by MIC values. The tetrahydrocarbazoles partly exceed the activity of the carbazole compounds and thus the activity of the used standard antibiotics. Thus, promising lead compounds could be identified for further studies. Full article

(This article belongs to the Special Issue Researches on Novel Antibacterial Agents)

► Show Figures

Scheme 1

24 pages, 8658 KB

Open AccessReview

Carbazole Derivatives as Antiviral Agents: An Overview

by Anna Caruso, Jessica Ceramella, Domenico Iacopetta, Carmela Saturnino, Maria Vittoria Mauro, Rosalinda Bruno, Stefano Aquaro and Maria Stefania Sinicropi

Molecules 2019, 24(10), 1912; https://doi.org/10.3390/molecules24101912 - 17 May 2019

Cited by 111 | Viewed by 9246

Abstract

Viruses represent the most common cause of infectious diseases worldwide and those with rapid propagation and high infection rates cause human and animal pandemics. These fast-spreading diseases are generally treated with antiviral drugs but, often, drug resistance occurs because of the ability of the pathogens to mutate rapidly and become less susceptible to the treatments. Even though new antivirals have been approved, e.g., in HIV (human immunodeficiency virus) and HCV (hepatitis C virus) therapeutic areas, the need to dispose of new pharmaceutical tools for the management of infections that still have no treatment is of growing interest. In these areas, carbazole represents an important privileged scaffold in drug discovery. Many compounds with a carbazolic core have been developed and some of them have shown antiviral activity. This review provides an overview on some already known carbazole derivatives, pointing the attention on the running progresses in identifying new molecules with carbazolic structure, that have shown interesting and encouraging in vitro and in vivo properties. These drugs may be exploited as valid alternatives in antiviral therapy. Full article

(This article belongs to the Special Issue Recent Advances in the Development of Antiviral Agents)

► Show Figures

Figure 1

1 pages, 87 KB

Open AccessShort Note

N-(5-Phenyl-2,4-pentadiynyl)-1,2,3,4-tetrahydrocarbazole

by Bruce A. Hathaway

Molecules 1998, 3(4), M75; https://doi.org/10.3390/M75 - 15 Apr 1998

Cited by 1 | Viewed by 2754

Abstract

Under nitrogen, 2.09g of N-propargyl-1,2,3,4-tetrahydrocarbazole [1], 0.2g of CuCl, 20 mL of 70% aqueous ethylamine, and 30 mL of 95% ethanol were combined and stirred.[...] Full article

(This article belongs to the Section Molbank Section of Molecules, 1997-2001)

Search Results (6)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI

Saved Queries

Search Filter Reset All

Years

Feature Papers

Subjects

Journals

Article Types

Countries / Regions

Search Results (6)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI