Synthesis and in vitro biological evaluation of 1,3-bis-(1,2,3-triazol-1-yl)-propan-2-ol derivatives as antifungal compounds fluconazole analogues

Zambrano-Huerta, Armando; Cifuentes-Castañeda, Damián David; Bautista-Renedo, Joanatan M.; Mendieta-Zerón, Hugo; Melgar‐Fernández, Roberto; Pavón-Romero, Sergio; Morales-Rodríguez, Macario; Frontana‐Uribe, Bernardo A.; González‐Rivas, Nelly; Cuevas-Yáñez, Erick

doi:10.1007/s00044-019-02317-5

Cited by 19 publications

(10 citation statements)

References 35 publications

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“…Development of Candida spp. resistance has also commonly been observed in HIV-infected patients who received prolonged FLC treatment for oropharyngeal candidiasis [2,10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Despite recent advances in antifungal chemotherapy, the mortality rates of invasive fungal infections have remained unchanged and there is a necessity for the development of new antifungal compounds. Aiming at new and effective antifungal drugs, our attention was focused on the azole derivatives because of their low toxicity, broad spectrum of activity, and favorable pharmacokinetic properties [10,11,14].…”

Section: Introductionmentioning

confidence: 99%

“…MCF-7 Cell Culture and In Vitro Assay for Inhibition of Metabolism of All-trans Retinoic Acid (ATRA) Human MCF-7 breast cancer cells were cultured in phenol red-free RPMI 1640 medium supplemented with 5% (v/v) charcoal free fetal calf serum, antibiotics (penicillin and streptomycin), and fungizone at the same concentration of 10 iU/mL (all reagents from Gibco Europe Ltd., Scotland, UK). Cells were grown in a humidified incubator (5% CO 2 , 95% air) at 37 • C. [11, H]All-trans-retinoic acid (37 MBq/mL) was purchased from PerkinElmer Life Science Ltd. (USA). All-trans retinoic acid, NADPH, butylated hydroxyanisole, and KTC were obtained from Sigma-Aldrich (Gillingham, UK).…”

mentioning

confidence: 99%

“…MCF-7 cells were seeded in 12-well cell culture plates (Cornings Inc., New York, USA) at 2.5 × 10 5 cells per well in a total volume of 1.5 mL. Cells were allowed to adhere to the well for 24 h. After 24 h, the medium from each well was removed, washed once with phosphate buffer saline (PBS), and replaced by fresh medium plus 10 µL inhibitor/solvent (acetonitrile) and 10 µL of ATRA (to give a final concentration of 1 × 10 −7 M ATRA and 0.1 µCi [11, H]all-trans-retinoic acid). The plates were foil wrapped and incubated at 37 • C for 9 h. Each treatment was performed in duplicate.…”

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confidence: 99%

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Synthesis, Optimization, Antifungal Activity, Selectivity, and CYP51 Binding of New 2-Aryl-3-azolyl-1-indolyl-propan-2-ols

Lebouvier

Pagniez

et al. 2020

Pharmaceuticals

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A series of 2-aryl-3-azolyl-1-indolyl-propan-2-ols was designed as new analogs of fluconazole (FLC) by replacing one of its two triazole moieties by an indole scaffold. Two different chemical approaches were then developed. The first one, in seven steps, involved the synthesis of the key intermediate 1-(1H-benzotriazol-1-yl)methyl-1H-indole and the final opening of oxiranes by imidazole or 1H-1,2,4-triazole. The second route allowed access to the target compounds in only three steps, this time with the ring opening by indole and analogs. Twenty azole derivatives were tested against Candida albicans and other Candida species. The enantiomers of the best anti-Candida compound, 2-(2,4-dichlorophenyl)-3-(1H-indol-1-yl)-1-(1H-1,2,4-triazol-1-yl)-propan-2-ol (8g), were analyzed by X-ray diffraction to determine their absolute configuration. The (−)-8g enantiomer (Minimum inhibitory concentration (MIC) = IC80 = 0.000256 µg/mL on C. albicans CA98001) was found with the S-absolute configuration. In contrast the (+)-8g enantiomer was found with the R-absolute configuration (MIC = 0.023 µg/mL on C. albicans CA98001). By comparison, the MIC value for FLC was determined as 0.020 µg/mL for the same clinical isolate. Additionally, molecular docking calculations and molecular dynamics simulations were carried out using a crystal structure of Candida albicans lanosterol 14α-demethylase (CaCYP51). The (−)-(S)-8g enantiomer aligned with the positioning of posaconazole within both the heme and access channel binding sites, which was consistent with its biological results. All target compounds have been also studied against human fetal lung fibroblast (MRC-5) cells. Finally, the selectivity of four compounds on a panel of human P450-dependent enzymes (CYP19, CYP17, CYP26A1, CYP11B1, and CYP11B2) was investigated.

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“…Development of Candida spp. resistance has also commonly been observed in HIV-infected patients who received prolonged FLC treatment for oropharyngeal candidiasis [2,10,11].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Synthesis, Optimization, Antifungal Activity, Selectivity, and CYP51 Binding of New 2-Aryl-3-azolyl-1-indolyl-propan-2-ols

Lebouvier

Pagniez

et al. 2020

Pharmaceuticals

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“…On preliminary results, the ethyl 7‐azide‐1‐ethyl‐6,8‐difluoroquinolone‐3‐carboxylate 1 , and ethyl 7‐azide‐1‐ethyl‐6‐fluoroquinolone‐3‐carboxylate 2 were prepared from 2,3,4‐trifluoro‐, or 3,4‐difluoro‐aniline, according to the literature method . Azide fluoroquinolone 1 , was first synthesized and used for the CuAAC by CuI and NaOH (0.5 N) . The Cu(I) species may either be introduced as performed complexes, but these conditions did not generate favorable results, even when a variety of solvents (MeOH, CH 3 CN, DMSO, DMF, H 2 O/acetone, H 2 O/CH 3 CN) were used in combination with other bases as DIPEA or TEA, or when the temperature was increased to 140 °C .…”

Section: Resultsmentioning

confidence: 99%

Copper(I)‐Catalyzed Azide‐Alkyne Cycloaddition Microwave‐Assisted: Preparation of 7‐(4‐Substituted‐1H‐1,2,3‐Triazol‐1‐yl)‐Fluoroquinolones

et al. 2019

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Nowadays, the pharmaceutical industry faces the challenge of innovating and increasing the productivity of new medicines due to the increasing multidrug resistance among bacteria, viruses and fungi. The main objective of the present study is connected quinolone and triazole molecules to enhance and broad antibacterial spectrum as well as to have multiple mechanisms of action. Preparation of 4‐substituted‐1H‐1,2,3‐triazol‐1‐yl in C‐7 of 6‐fluoro‐ and 6,8‐difluoro‐quinolone ring is showed. The synthesis involved the preparation of intermediate ethyl 7‐azide‐1‐ethyl‐fluoroquinolone‐3‐carboxylate, followed by copper(I)‐catalyzed azide‐alkyne cycloaddition to give 13 derivatives. The cycloaddition was carried out by two different methods, where it was observed that the microwave radiation was the best reaction condition, obtaining a range of yields of 47–93%, at 140 °C, 125Wmax for 10 minutes. Therefore, this methodology provided an easy pathway to synthesize a library of fluoroquinolones coupled to 1,2,3‐triazole, still unexplored.

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1,2,3‐Triazole Derivatives as an Emerging Scaffold for Antifungal Drug Development against Candida albicans: A Comprehensive Review

Singh

Sharma

et al. 2023

Chemistry & Biodiversity

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Candida infections are most prominent among fungal infections majorly target immunocompromised and hospitalized patients and cause significant morbidity and mortality. Candida albicans is the notorious and most prevalent among all pathogenic Candida strains. Its emerging resistance toward available antifungal agents making it hard to tackle and emerging as global healthcare emergency. Simultaneously, 1,2,3-triazole nucleus is a privileged scaffold that is gaining importance in antifungal drug development due to being a prominent bioactive linker and isostere of triazole based antifungal class core 1,2,4-triazole. Numerous reports have been updated in scientific literature in last few decades related to utilization of 1,2,3-triazole nucleus in antifungal drug development against Candida albicans. Present review will shed light on various preclinical studies focused on development of 1,2,3-triazole derivatives targeting Candida albicans along with brief highlight on clinical trials and newly approved drugs. Structure-activity relationship has been precisely discussed for each architect along with future perspective that will help medicinal chemists in design and development of potent antifungal agents for tackling infections derived from Candida albicans.

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Synthesis and in vitro biological evaluation of 1,3-bis-(1,2,3-triazol-1-yl)-propan-2-ol derivatives as antifungal compounds fluconazole analogues

Cited by 19 publications

References 35 publications

Synthesis, Optimization, Antifungal Activity, Selectivity, and CYP51 Binding of New 2-Aryl-3-azolyl-1-indolyl-propan-2-ols

Synthesis, Optimization, Antifungal Activity, Selectivity, and CYP51 Binding of New 2-Aryl-3-azolyl-1-indolyl-propan-2-ols

Copper(I)‐Catalyzed Azide‐Alkyne Cycloaddition Microwave‐Assisted: Preparation of 7‐(4‐Substituted‐1H‐1,2,3‐Triazol‐1‐yl)‐Fluoroquinolones

1,2,3‐Triazole Derivatives as an Emerging Scaffold for Antifungal Drug Development against Candida albicans: A Comprehensive Review

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