Pyridazine-based heteroleptic copper(II) complexes as potent anticancer drugs by inducing apoptosis and S-phase arrest in breast cancer cell

Rafi, Ummer Muhammed; Mahendiran, Dharmasivam; Devi, Venkat Gayathri; Doble, Mukesh; Rahiman, A. Kalilur

doi:10.1016/j.ica.2018.06.007

Cited by 13 publications

(6 citation statements)

References 52 publications

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“…Interestingly, the complexes showed less cytotoxicity effects on the normal cell line (NHDF) than the cancer cell lines; hence these may be useful in selectively targeting cancer cells over normal cells. The most notable results were obtained for complex 2 , which is better than the commonly used drug cisplatin against all the tested cancer cell lines and metal(II) complexes derived from pyridazine‐based ligands reported in the literature . The higher anti‐proliferative activity of copper(II) complex 2 may be due to the presence of electron‐releasing diethylamino group.…”

Section: Resultsmentioning

confidence: 87%

“…The IR spectra of the copper(II) complexes revealed the coordination of phenolate oxygen, azomethine and pyridazine nitrogens of pyridazine‐based ligands, and the carboxylate and carbonyl oxygens of ciprofloxacin to the copper(II) ion (Table S1; Figure S1). The stretching vibrations of azomethine group ( ν (C═N), 1622–1631 cm −1 ), phenolic group ( ν (C─O), 1282–1292 cm −1 ) and pyridazine ring nitrogens ( ν (N═N), 1526–1535 cm −1 ) for HL 1–3 were observed with considerable shifts at 1603–1614, 1244–1251 and 1550–1591 cm −1 , respectively, for the complexes . Ciprofloxacin shows two strong absorption bands at 1725 and 1630 cm −1 due to ʋ (COOH) and ʋ (C═O) stretching vibrations, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Pyridazolato‐bridged copper(II) complexes also exhibited anti‐proliferative and apoptosis‐inducing effects against oestrogen‐independent breast (BT‐20) and androgen‐independent prostate (PC‐3) cancer cells . More recently, our group has reported the anticancer activity of metal(II) complexes of pyridazine‐based tridentate N‐donor ligands against breast cancer (MDA‐MB‐231) cell line . In the study presented here, we chose pyridazine‐based ligands and ciprofloxacin to synthesize heteroleptic copper(II) complexes in order to investigate their in vitro anti‐proliferative activity against three human cancer cell lines and one non‐cancer cell line.…”

Section: Introductionmentioning

confidence: 99%

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In vitro anti‐proliferative and in silico docking studies of heteroleptic copper(II) complexes of pyridazine‐based ligands and ciprofloxacin

Rafi¹,

Mahendiran

Rahiman³

2019

Applied Organom Chemis

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Three heteroleptic copper(II) complexes of the type [Cu(L1–3)(cf)(ClO4)] (1–3), where cf = ciprofloxacin, have been synthesized using pyridazine‐based ligands 3‐chloro‐6‐(salicylidenehydrazinyl)pyridazine (HL1), 3‐chloro‐6‐(4‐diethylaminosalicylidenehydrazinyl)pyridazine (HL2) and 3‐chloro‐6‐(5‐bromosalicylidenehydrazinyl)pyridazine (HL3). Electronic spectral data and magnetic moment values suggest octahedral geometry for the synthesized copper(II) complexes. Electrochemical data of the copper(II) complexes present an irreversible one‐electron reduction wave in the cathodic potential region (Epc) between −0.631 and −0.670 V. Frontier molecular orbital calculations were carried out, and the obtained low‐energy gap supports the bio‐efficacy of the complexes. All the complexes were screened for their in vitro cytotoxicity activity against three human cancerous (breast adenocarcinoma (MCF‐7), hepatoma (HepG‐2) and cervical (HeLa)) and one non‐cancerous (non‐tumorigenic human dermal fibroblast (NHDF)) cell lines using MTT assay, in which complex 2 exhibited higher activity. The apoptosis induction by the complexes was analysed using the Hoechst dye staining method with MCF‐7 cell line, which indicates higher apoptotic activity of complex 2. A molecular docking study was carried out to ascertain the binding affinity of the synthesized heteroleptic copper(II) complexes with phosphoinositide 3‐kinase gamma (PI3Kγ) receptor.

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Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vitro anti‐proliferative and in silico docking studies of heteroleptic copper(II) complexes of pyridazine‐based ligands and ciprofloxacin

Rafi¹,

Mahendiran

Rahiman³

2019

Applied Organom Chemis

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“…The apoptosis induced by the complex in the MCF-7 cell line was analyzed by Hoechst staining, which indicated that the complex had high apoptotic activity. Therefore, copper(II) complexes have anti-tumor effects by causing DNA damage and inducing apoptosis ( Figure 6 B) [ 68 ]. Gu et al prepared four terpyridine copper(II) complexes ( Figure 6 C), which exhibited higher cytotoxic activity against several tested cancer cell lines, especially BEL-7402 cells.…”

Section: Application Of Novel Copper Complexes In Tumor Therapymentioning

confidence: 99%

Potential of Copper and Copper Compounds for Anticancer Applications

Wang

Chen

et al. 2023

Pharmaceuticals

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Inducing cancer cell death has always been a research hotspot in life sciences. With the continuous deepening and diversification of related research, the potential value of metal elements in inducing cell death has been explored. Taking iron as an example, ferroptosis, mainly characterized by increasing iron load and driving the production of large amounts of lipid peroxides and eventually leading to cell death, has recently attracted great interest in the cancer research community. After iron, copper, a trace element, has received extensive attention in cell death, especially in inducing tumor cell death. Copper and its complexes can induce autophagy or apoptosis in tumor cells through a variety of different mechanisms of action (activation of stress pathways, arrest of cell cycle, inhibition of angiogenesis, cuproptosis, and paraptosis), which are promising in cancer therapy and have become new hotspots in cancer treatment research. This article reviews the main mechanisms and potential applications of novel copper and copper compound-induced cell death, focusing on copper compounds and their anticancer applications.

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“…On other hand, the chemical and biological studies of pyridazine derivatives have been of great interest for many years for medicinal and agricultural reasons due to their large spectrum of biological properties including antimicrobial [ 3 , 4 ], antileishmania [ 5 ], antiviral [ 6 ], anticancer [ 7 ], anti-tubercular [ 8 ], analgesic and anti-inflammatory [ 9 , 10 ], anti-Alzheimer [ 11 ], antihypertensive [ 12 ], and anticonvulsant activities [ 13 ]. A substantial number of pyridazinones have been reported to possess a wide variety of agrochemicals such as pesticides [ 14 , 15 , 16 , 17 ] and recently, several pyridazinone derivatives have been reported as potent antibacterial agents ( Figure 1 , compound A) [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives

et al. 2023

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In this work, a novel series of pyridazinone derivatives (3–17) were synthesized and characterized by NMR (1H and 13C), FT-IR spectroscopies, and ESI-MS methods. All synthesized compounds were screened for their antibacterial activities against Staphylococcus aureus (Methicillin-resistant), Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, and Acinetobacter baumannii. Among the series, compounds 7 and 13 were found to be active against S. aureus (MRSA), P. aeruginosa, and A. baumannii with the lowest MIC value range of 3.74–8.92 µM. Afterwards, DFT calculations of B3LYP/6-31++G(d,p) level were carried out to investigate geometry structures, frontier molecular orbital, molecular electrostatic potential maps, and gap energies of the synthesized compounds. In addition, the activities of these compounds against various bacterial proteins were compared with molecular-docking calculations. Finally, ADMET studies were performed to investigate the possibility of using of the target compounds as drugs.

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Pyridazine-based heteroleptic copper(II) complexes as potent anticancer drugs by inducing apoptosis and S-phase arrest in breast cancer cell

Cited by 13 publications

References 52 publications

In vitro anti‐proliferative and in silico docking studies of heteroleptic copper(II) complexes of pyridazine‐based ligands and ciprofloxacin

In vitro anti‐proliferative and in silico docking studies of heteroleptic copper(II) complexes of pyridazine‐based ligands and ciprofloxacin

Potential of Copper and Copper Compounds for Anticancer Applications

Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives

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