Recent Trends in Drug Development for the Treatment of Adenocarcinoma Breast
Cancer: Thiazole, Triazole, and Thiosemicarbazone Analogues as Efficient Scaffolds

Scarim, Cauê Benito; Chin, Chung Man

doi:10.2174/1871520621666211201152815

Cited by 5 publications

(6 citation statements)

References 174 publications

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“…[25][26][27][28][29] These ligands, and many of their metallic compounds have shown featured antimicrobial, antiviral, antiparasitic, and antineoplastic activities. [28,30,31] TSCs can be functionalized with diverse bioactive or pharmacophoric groups and have been amply studied in medicinal chemistry [31,32] including clinical trials for multiple cancers (NCT02595879, NCT02688101, and NCT02433626). [19,33] Studies have shown that the anti-tumor activity of the thiosemicarbazones is due to their ability to act by multiple mechanisms of action, [34][35][36][37][38][39][40] such as inhibition of DNA synthesis, inhibition of cell proliferation, cell cycle, angiogenesis and metastasis, and modulation of signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Their electronic structure is characterized by π‐delocalization [25–29] . These ligands, and many of their metallic compounds have shown featured antimicrobial, antiviral, antiparasitic, and antineoplastic activities [28,30,31] . TSCs can be functionalized with diverse bioactive or pharmacophoric groups and have been amply studied in medicinal chemistry [31,32] including clinical trials for multiple cancers (NCT02595879, NCT02688101, and NCT02433626) [19,33] .…”

Section: Introductionmentioning

confidence: 99%

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5‐Nitrofuryl‐Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity

Rodríguez‐Arce,

Gavrilov,

Alvite

et al. 2023

ChemPlusChem

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This work describes the synthesis of four gold(I) [AuClL] compounds containing chloro and biologically active protonated thiosemicarbazones based on 5‐nitrofuryl (L=HSTC). The stability of the compounds in dichloromethane, DMSO, and DMSO/culture media solutions was investigated by spectroscopy, cyclic voltammetry, and conductimetry, indicating the formation overtime of cationic monometallic [Au(HTSC)(DMSO)]± or [Au(HTSC)2]±, and/or dimeric species. Neutral [{Au(TSC)}2] species were obtained from one of the compounds in dichlomethane/n‐hexane solution and characterized by X‐ray crystallography revealing a Au−Au bond, and deprotonated thiosemicarbazone (TSC). The cytotoxicity of the gold compounds and thiosemicarbazone ligands was evaluated against selected cancer cell lines and compared to that of Auranofin. Studies of the most stable, cytotoxic, and selective compound on a renal cancer cell line (Caki‐1) demonstrated its relevant antimigratory and anti‐angiogenic properties, and preferential accumulation in the cell nuclei. Its mode of action seems to involve interaction with DNA, and subsequent cell death via apoptosis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

5‐Nitrofuryl‐Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity

Rodríguez‐Arce,

Gavrilov,

Alvite

et al. 2023

ChemPlusChem

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“…The thiosemicarbazone compounds used in clinical research include acetamidobenzaldehyde semicarbazide ( 1 ), N-methylisatin thiosemicarbazone ( 2 ), 5-hydroxy-2-methylcarbamate acylpyridine thiosemicarbazide ( 3 ), 3-aminopyridine-2-carbaldehyde thiosemicarbazide ( 4 ), COTI-2 ( 5 ), bis-2-pyridyl ketone 4-cyclohexyl-4-methyl-3-thiosemicarbazide ( 6 ) ( Scheme 1 ) ( Summers, 2019a ; Matesanz et al, 2021a ; Scarim and Chin, 2022a ). Triapine is the most prevalent anti-cancer agent and has been included in over 20 clinical trials for treating multiple cancers, including pancreatic cancer, non-small cell lung cancer (NSCLC), leukaemia and myeloproliferative diseases ( Scarim and Chin, 2022a ). However, some tumour types respond poorly to Triapine, developing serious side effects, such as hyperhemoglobinemia ( Yu et al, 2006 ; Yu et al, 2009 ).…”

Section: Thiosemicarbazone Ligands In a Clinical Trialmentioning

confidence: 99%

“…It was established that thiosemicarbazides were metal chelators before the discovery of their anti-tumour activity. In addition to the presence of the C=N and C=S bonds in their own structure, which is favourable for metal coordination, it possesses a flexible thiourea structure that can introduce different substituents or functional groups ( Scarim and Chin, 2022a ). Especially for various heterocyclic ligands, introducing more heteroatoms enriches thiosemicarbazone’s coordination mode and enhances its coordination ability ( Stefani et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Advances in thiosemicarbazone metal complexes as anti-lung cancer agents

Bai

Zheng²,

Qi³

2022

Front. Pharmacol.

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The great success of cisplatin as a chemotherapeutic agent considerably increased research efforts in inorganic biochemistry to identify more metallic drugs having the potential of treating lung cancer. Metal coordination centres, which exhibit a wide range of coordination numbers and geometries, various oxidised and reduced states and the inherent ligand properties offer pharmaceutical chemists a plethora of drug structures. Owing to the presence of C=N and C=S bonds in a thiosemicarbazone Schiff base, N and S atoms in its hybrid orbital has lone pair of electrons, which can generate metal complexes with different stabilities with most metal elements under certain conditions. Such ligands and complexes play key roles in the treatment of anti-lung cancer. Research regarding metallic anti-lung cancer has advanced considerably, but there remain several challenges. In this review, we discuss the potential of thiosemicarbazone Schiff base complexes as anti-lung cancer drugs, their anti-cancer activities and the most likely action mechanisms involving the recent families of copper, nickel, platinum, ruthenium and other complexes.

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“…Thiosemicarbazones (TSCs) and their corresponding metal complexes occupy a prominent place in medicinal chemistry and are well-known for their pharmacological activities [ 22 , 23 , 24 , 25 ]. The mechanisms by which TSC derivatives exert their antiproliferative effects against cancer cell lines have been linked to various biological activities including ribonucleotide reductase [ 26 , 27 , 28 ] or topoisomerase II [ 29 , 30 ] inhibition, ROS production [ 31 , 32 , 33 ] and mitochondria homeostasis alteration [ 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Transcription Profile Induced by Antiproliferative Thiosemicarbazone Metal Complexes in U937 Cancer Cells

et al. 2023

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Since the discovery of cisplatin, the search for metal-based compounds with therapeutic potential has been a challenge for the scientific community. In this landscape, thiosemicarbazones and their metal derivatives represent a good starting point for the development of anticancer agents with high selectivity and low toxicity. Here, we focused on the action mechanism of three metal thiosemicarbazones [Ni(tcitr)2], [Pt(tcitr)2], and [Cu(tcitr)2], derived from citronellal. The complexes were already synthesized, characterized, and screened for their antiproliferative activity against different cancer cells and for genotoxic/mutagenic potential. In this work, we deepened the understanding of their molecular action mechanism using an in vitro model of a leukemia cell line (U937) and an approach of transcriptional expression profile analysis. U937 cells showed a significant sensitivity to the tested molecules. To better understand DNA damage induced by our complexes, the modulation of a panel of genes involved in the DNA damage response pathway was evaluated. We analyzed whether our compounds affected cell cycle progression to determine a possible correlation between proliferation inhibition and cell cycle arrest. Our results demonstrate that metal complexes target different cellular processes and could be promising candidates in the design of antiproliferative thiosemicarbazones, although their overall molecular mechanism is still to be understood.

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Recent Trends in Drug Development for the Treatment of Adenocarcinoma Breast Cancer: Thiazole, Triazole, and Thiosemicarbazone Analogues as Efficient Scaffolds

Cited by 5 publications

References 174 publications

5‐Nitrofuryl‐Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity

5‐Nitrofuryl‐Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity

Advances in thiosemicarbazone metal complexes as anti-lung cancer agents

Modulation of Transcription Profile Induced by Antiproliferative Thiosemicarbazone Metal Complexes in U937 Cancer Cells

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