In vitro and in vivo biological activities of azulene derivatives with potential applications in medicine

Abstract

Azulene is an aromatic hydrocarbon that possesses a unique chemical structure and interesting biological properties. Azulene derivatives, including guaiazulene or chamazulene, occur in nature as components of many plants and mushrooms, such as Matricaria chamomilla, Artemisia absinthium, Achillea millefolium, and Lactarius indigo. Due to physicochemical properties, azulene and its derivatives have found many potential applications in technology, especially in optoelectronic devices. In medicine, the ingredients of these plants have been widely used for hundreds of years in antiallergic, antibacterial, and anti-inflammatory therapies. Herein, the applications of azulene, its derivatives and their conjugates with biologically active compounds are presented. The potential use of these compounds concerns various areas of medicine, including anti-inflammatory with peptic ulcers, antineoplastic with leukemia, antidiabetes, antiretroviral with HIV-1, antimicrobial, including antimicrobial photodynamic therapy, and antifungal.

Tumor-Specificity, Neurotoxicity, and Possible Involvement of the Nuclear Receptor Response Pathway of 4,6,8-Trimethyl Azulene Amide Derivatives

“…Their tumor-specificity was matched at a higher probability with the onset of a signaling pathway of NFκB, and receptors for estrogen, thyroid stimulating hormone, and glucocorticoid ( Figure 7 ). This is consistent with the reported anti-inflammatory activity of guaiazulene [ 4 , 9 , 20 , 21 , 22 ]. On the other hand, the involvement of other signaling pathways such as caspase and androgen receptor ( Figure S7 ), transforming growth factor β (TGFβ), peroxisome proliferator activated receptor δ (PPARδ), endoplasmic reticulum stress (ER stress) response, and retinoid X receptor-α(RXR) ( Figure S8 ) seems to be low.…”

“…Azulene derivatives, including guaiazulene ( Figure S1A ), are present in many plants and mushrooms, and applied as optoelectronic devices and ingredients used for hundreds of years in antiallergic, antibacterial, and anti-inflammatory therapies [ 4 ]. Several research studies have reported the applications of azulenes on oral diseases.…”

Fungal Endophytes: A Potential Source of Antibacterial Compounds

“…The introspection of the spectrum of the volatile organic mixture from different Muscodor species has revealed the antibacterial spectrum of some commonly occurring entities such as isobutyric acid [209][210][211], β-bisabolol and azulene and its derivatives [212]. Thus, creating artificial mixtures and evaluating them for their anti-bacterial activities may prove to be very useful for preventing drug-resistant film-forming bacteria from causing infections in clinical as well as non-clinical settings.…”

Challenging Approach to the Development of Novel Estrogen Receptor Modulators Based on the Chemical Properties of Guaiazulene

“…It has been suggested that the hydrophobic structure and the dihedral angle of the two benzene rings are important for the development of ERα antagonists or ERα partial agonists. Guaiazulene and its derivatives (Figure 2) are widely used in pharmaceuticals and cosmetics because of their moderate anti-inflammatory activities [16]. Azulene, the central skeleton of guaiazulene, is a typical non-benzene aromatic compound that has a fused-ring structure composed of cyclopentadiene and cycloheptatriene [17].…”