Modification of 7-piperazinylquinolone antibacterials to promising anticancer lead compounds: Synthesis and in vitro studies

Ahadi, Hamideh; Emami, Saeed

doi:10.1016/j.ejmech.2019.111970

Cited by 35 publications

(16 citation statements)

References 67 publications

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“…Piperazinylquinolone 70 (Figure 35) was considered a starting point for the design and development of new anticancer agents. Chemical modification of N-4 in the piperazine ring and the carboxylic acid at C-3 could present sufficient flexibility 96 .…”

Section: Biological Effects Of Natural Products Containing the Piperazinyl Moietymentioning

confidence: 99%

Piperazine skeleton in the structural modification of natural products: a review

Zhang

Guo

Deng

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Piperazine moiety is a cyclic molecule containing two nitrogen atoms in positions 1 and 4, as well as four carbon atoms. Piperazine is one of the most sought heterocyclics for the development of new drug candidates with a wide range of applications. Over 100 molecules with a broad range of bioactivities, including antitumor, antibacterial, anti-inflammatory, antioxidant, and other activities, were reviewed. This article reviewed investigations regarding piperazine groups for the modification of natural product derivatives in the last decade, highlighting parameters that affect their biological activity.

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Section: Biological Effects Of Natural Products Containing the Piperazinyl Moietymentioning

confidence: 99%

Piperazine skeleton in the structural modification of natural products: a review

Zhang

Guo

Deng

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…[3] They are also used as antifungal, antibiotic, anticancer, antibacterial, anti-apoptotic, anticoagulant, anti-inflammatory, antidiabetic, antipsychotic, and anxiolytic agents. [4][5][6][7][8][9] Quinolinones metal complexes have a substantial importance in the coordination chemistry as a result of their industrial and biological applications. These complexes exhibited promising bio-efficiency, especially as antimicrobial and anti-tumor agents.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and structural characterization of nano‐sized metal complexes of 3‐(1‐methyl‐4‐hydroxy‐2‐oxo‐1,2‐dihydroquinolin‐3‐yl)‐2‐nitro‐3‐oxopropanoic acid. XRD, thermal, 3D modeling, and antitumor activity studies

El-ghamry

El‐Shafiy

2021

Applied Organom Chemis

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New Co(II), Ni(II), Cu(II), Zn(II), and Fe(III) complexes of the ligand 3-(1-methyl-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-2-nitro-3-oxopropanoic acid (H 3 L) were synthesized and characterized by various analytical and spectroscopic techniques. The obtained data confirmed the formation of 1:1 (M:L) stoichiometry for Fe(III), Co(II) complexes and 2:1 (M:L) stoichiometry for Ni(II), Cu(II), Zn(II) complexes, and the ligand, H 3 L, acts as mono-, bi-, tribasic bis-, tris-and tetradentate towards the metal ions via the oxygen of quinolinonate, the enolic/ketonic of β-ketoacid, and carboxylate besides of the nitro groups. All complexes showed tetrahedral geometry, except Fe(III) complex which exhibited an octahedral geometry. The X-ray diffractograms of the ligand, H 3 L, and its metal complexes revealed a series of sharp and intense diffraction peaks which indicate their crystalline characteristic with the particle size in the nano-scale range. Geometrical optimizations of the ligand, H 3 L, and its metal complexes were performed at the B3LYP/6-311G(d, p) level using density functional theory (DFT) implemented in the Gaussian 09 program.The data obtained were correlated with the experimental results and suggested that the Zn(II) complex may exhibit extremely bio-efficiency than other compounds. The antimicrobial screening results showed enhancement in the efficiency of the free ligand, H 3 L, on coordination with the metal ions. The antitumor activity was evaluated in vitro against Hepatocellular carcinoma cell line (HepG-2 cells). The ligand, H 3 L, and its Zn(II) complex showed strong antitumor activities, especially nano-sized Zn(II) complex that exhibited IC 50 value (2.90 μg/ml) smaller than the well-known standard antitumor drug cisplatin (IC 50~3 .27 μg/ml), prominent it as an antitumor agent towards HepG-2 cells.

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“…In this regard, the structural modifications required for anticancer activity of CP have been clearly discussed 1 , 27 . Bio-isosteric replacement of the carboxylic group at C-3 of CP with tetrazole heterocyclic ring markedly improves its anti-proliferative activity 1 , 28 . Also, one key modification was carried out by substituting its N -4 piperazine heterocycle moiety with an aryl or heteroaryl bulky group 1 , 27 .…”

Section: Introductionmentioning

confidence: 99%

New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization

Mohammed

El-Hafeez

Ebeid

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of novel 1,2,3-triazole-linked ciprofloxacin-chalcones 4a-j were synthesised as potential anticancer agents. Hybrids 4a-j exhibited remarkable anti-proliferative activity against colon cancer cells. Compounds 4a-j displayed IC 50 s ranged from 2.53-8.67 µM, 8.67–62.47 µM, and 4.19–24.37 µM for HCT116, HT29, and Caco-2 cells; respectively, whereas the doxorubicin, showed IC 50 values of 1.22, 0.88, and 4.15 µM. Compounds 4a, 4b, 4e, 4i, and 4j were the most potent against HCT116 with IC 50 values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC 50 = 1.22 µM). Also, hybrids 4a, 4b, 4e, 4i, and 4j exhibited remarkable inhibitory activities against topoisomerase I, II, and tubulin polymerisation. They increased the protein expression level of γH2AX, indicating DNA damage, and arrested HCT116 in G2/M phase, possibly through the ATR/CHK1/Cdc25C pathway. Thus, the novel ciprofloxacin hybrids could be exploited as potential leads for further investigation as novel anticancer medicines to fight colorectal carcinoma.

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Modification of 7-piperazinylquinolone antibacterials to promising anticancer lead compounds: Synthesis and in vitro studies

Cited by 35 publications

References 67 publications

Piperazine skeleton in the structural modification of natural products: a review

Piperazine skeleton in the structural modification of natural products: a review

Synthesis and structural characterization of nano‐sized metal complexes of 3‐(1‐methyl‐4‐hydroxy‐2‐oxo‐1,2‐dihydroquinolin‐3‐yl)‐2‐nitro‐3‐oxopropanoic acid. XRD, thermal, 3D modeling, and antitumor activity studies

New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization

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