Discovery of tropinone-thiazole derivatives as potent caspase 3/7 activators, and noncompetitive tyrosinase inhibitors with high antiproliferative activity: Rational design, one-pot tricomponent synthesis, and lipophilicity determination

Piechowska, Katarzyna; Świtalska, Marta; Cytarska, Joanna; Jaroch, Karol; Łuczykowski, Kamil; Chałupka, Joanna; Wietrzyk, Joanna; Misiura, Konrad; Bojko, Barbara; Kruszewski, Stefan; Łączkowski, Krzysztof Z.

doi:10.1016/j.ejmech.2019.05.006

Cited by 38 publications

(24 citation statements)

References 22 publications

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“…Different studies also confirmed the role of TYR in neurodegenerative and autoimmune disorders (Lavezzo et al, 2016;Neagu et al, 2018;Piechowska et al, 2019).…”

Section: Introductionmentioning

confidence: 70%

Design, synthesis, in vitro and in silico studies of novel Schiff base derivatives of 2‐hydroxy‐4‐methoxybenzamide as tyrosinase inhibitors

Iraji

Panahi

Khoshneviszadeh

et al. 2020

Drug Development Research

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Due to the fact that tyrosinase is responsible for biosynthesis and regulation of melanins and browning food products, tyrosinase inhibitors can be favorable agents in cosmetics and medicinal industries. A series of novel 2-hydroxy-4-methoxybenzohydrazide were designed, synthesized, and their new application as tyrosinase inhibitors was also disclosed. Based on in vitro tyrosinase inhibitory assay, 4d as the strongest inhibitor of tyrosinase with an IC 50 value of 7.57 μM showed approximately 2.5-fold better inhibition than kojic acid as positive control followed by two compounds 4b (IC 50 = 8.19 ± 0.25 μM) and 4j (IC 50 = 8.92 ± 0.016) which displayed preferable tyrosinase inhibitory activity. Detailed investigations on the mechanism of action of the 4d reported mix type of inhibition. More importantly, molecular modeling assessments proposed the ability of 4d for potential interaction with Cu (metal)-His (residue) within tyrosinase active site. Overall, 4d is a promising candidate for the development of anti-tyrosinase agents.

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“…Different studies also confirmed the role of TYR in neurodegenerative and autoimmune disorders (Lavezzo et al, 2016;Neagu et al, 2018;Piechowska et al, 2019).…”

Section: Introductionmentioning

confidence: 70%

Design, synthesis, in vitro and in silico studies of novel Schiff base derivatives of 2‐hydroxy‐4‐methoxybenzamide as tyrosinase inhibitors

Iraji

Panahi

Khoshneviszadeh

et al. 2020

Drug Development Research

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“…Scheme 2. Synthetic route for preparation of 1,2,3-1H-triazoles derivatized 4H-pyrano [2,3-d] pyrimidine analogs [2]; Reagents and conditions: (a) Ammonium solution 25%, 25 C, 3 h, or Cu@MOF-5 (10 mol%), 96% EtOH, 50 Inhibition of tumoral carbonic anhydrases (CA) could lead to slowdown of metastasis and reduced cancer symptoms. However, most of the discovered CA inhibitors have also inhibited isoforms of CA and thereby reduced efficiencies are observed.…”

Section: 23-1h-triazoles-linked 4h-pyrano [23-d] Pyrimidinementioning

confidence: 99%

“…Although the inhibitory activity is not up to the mark compared to previously designed derivatives, two compounds have succeeded to display significant activity. In that compound 137b (IC 50…”

Section: C-β-d-glucopyranosyl Azole Derivativesmentioning

confidence: 99%

Synthesis, pharmacological evaluation and structure-activity relationship of recently discovered enzyme antagonist azoles

Dorababu¹

2020

Heliyon

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Global people are suffering from the legion of diseases. Cytotoxic property of the chemical compound would not solely influence effective drug properties and reduce unnecessary side effects. Proteins/enzymes responsible for microbe proliferation or survival are specifically targeted and inhibited successfully making the cells to undergo apoptosis. Furthermore, isoforms of essential enzymes have distinct physiological functions; thereby inhibition of essential enzyme isoforms is an apt way to the clinical approach of disease neutralization. Drugs are designed so as to play significant roles such as signaling pathways in the oncogenic process including cell proliferation, invasion, and angiogenesis. The present review comprises collective information of the recent synthesis of various organic drug compounds in brief, which could inhibit particular enzyme. The review also covers the correlation of the structure of a drug molecule designed and its inhibitory activity. Also, the most significant enzyme inhibitors are highlighted and structural moieties/core units responsible for remarkable inhibitory values are emphasized.

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“…The last years of the research have confirmed that thiazole scaffold has diverse biological properties that can be used to treat many diseases, such as microbial infections (Bikobo et al 2017;Secci et al 2012;Łączkowski et al 2018a, 2018bZaki et al 2018;Ansari et al 2018), Parkinson's disease (Carradori et al 2018), cancer (de Santana et al 2018;Łączkowski et al 2014, 2016a, 2016bPiechowska et al 2019;Gomha et al 2018), epilepsy (Siddiqui and Ahsan 2010;Ahangar et al 2011;Łączkowski et al 2016a, 2016b, toxoplasmosis (Schultz et al 2014;Łączkowski et al 2018a, 2018b, and antioxidants (Geronikaki et al 2013;Djukic et al 2018). Considering the above-mentioned findings, we decided to design and synthesize the structure of hybrids incorporating both the thiazole ring and the cyclohexenyl moiety.…”

Section: Introductionmentioning

confidence: 98%

Synthesis, antimicrobial activity, and determination of the lipophilicity of ((cyclohex-3-enylmethylene)hydrazinyl)thiazole derivatives

et al. 2019

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Synthesis and investigation of antimicrobial activity of fifteen novel thiazoles containing cyclohexene moiety are presented. Among the derivatives, compounds 3a-3d, 3f, 3n, and 3o showed very strong activity against the reference Candida spp. strains with MIC = 0.015-3.91 µg/ml. The activity of these compounds is similar and even higher than the activity of nystatin used as positive control. Compounds 3d, 3f, 3n, 3o showed the highest activity with very strong effect towards most of yeasts isolated from clinical materials with MIC = 0.015-7.81 µg/ml. The cytotoxicity studies for the most active compounds showed that Candida spp. growth was inhibited at noncytotoxic concentrations for the mammalian L929 fibroblast. In addition, a good correlation was obtained between lipophilicity of compounds determined using reversed phase thin-layer chromatography and their antifungal activity.

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Discovery of tropinone-thiazole derivatives as potent caspase 3/7 activators, and noncompetitive tyrosinase inhibitors with high antiproliferative activity: Rational design, one-pot tricomponent synthesis, and lipophilicity determination

Cited by 38 publications

References 22 publications

Design, synthesis, in vitro and in silico studies of novel Schiff base derivatives of 2‐hydroxy‐4‐methoxybenzamide as tyrosinase inhibitors

Design, synthesis, in vitro and in silico studies of novel Schiff base derivatives of 2‐hydroxy‐4‐methoxybenzamide as tyrosinase inhibitors

Synthesis, pharmacological evaluation and structure-activity relationship of recently discovered enzyme antagonist azoles

Synthesis, antimicrobial activity, and determination of the lipophilicity of ((cyclohex-3-enylmethylene)hydrazinyl)thiazole derivatives

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