Novel fluconazole derivatives with promising antifungal activity

Abstract

The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activity of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against mammalian cells. The best compounds from our study exhibited broad-spectrum activity against most of the fungal strains tested, with excellent MIC values against a number of clinical isolates. The most promising compounds were found to be less hemolytic than the least hemolytic FDA-approved azole antifungal agent voriconazole (VOR). Finally, we demonstrated that the synthetic alkyl-amino FLC analogues displayed chain-dependent fungal membrane disruption as well as inhibition of ergosterol biosynthesis as possible mechanisms of action.

Biologically active metabolite(s) from haemolymph of red-headed centipede Scolopendra subspinipes possess broad spectrum antibacterial activity

“…Exact structure: bactericidal activity against Staphylococcus aureus and Escherichia coli (Niu et al 2018; Savage Paul 2017), pesticidal activity (Park et al 2018), anti-inflammatory activity (Wrasidlo and Natala 2018), antifungal activity against Candida and Aspergillus species by inhibiting ergosterol synthesis (Chandrika, et al 2018; Garneau-Tsodikova et al 2018), used as a component in traditional Chinese medicine for the treatment of Coronary heart disease complicated with depression (Zhang et al 2018a, b)…”

Essential Oil-Based Design and Development of Novel Anti-Candida Azoles Formulation

“…Azole derivatives show great potential activities against Candida infections. Chandrika et al developed 12 novel azole derivatives that showed significant antifungal activities against different types of Candida spp., but none of them was C. auris [22]. Similarly, Shrestha et al, successfully developed some novel alkylated-azoles that showed great activities against 13 clinically fungal isolates, but C. auris was not one of them [23].…”

Iron Pathways and Iron Chelation Approaches in Viral, Microbial, and Fungal Infections

“…Fungal Features— Cryptococcus neoformans , a basidiomycete fungus involved in meningitis, can lead to a poor outcome in patients who are immunocompromised [ 160 ]. The treatments are limited to anti-fungal agents such as amphotericin B (which binds to sterol in fungal cell membranes, leading to pore formation and ultimately fungal death [ 161 ]) and fluconazole (which disrupts the fungal membrane and ergosterol synthesis) [ 162 ]). However, these drugs elicit side effects including kidney damage [ 160 ] and thus, other agents are needed to improve treatment responses.…”