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The present study established thirteen novel 8-hydroxyquinoline/chalcone hybrids3a-mof hopeful anticancer activity. According to NCI screening and MTT assay results, compounds3d-3f, 3i,3k,and3ldisplayed potent growth inhibition on HCT116 and MCF7 cells compared to Staurosporine. Among these compounds,3eand3fshowed outstanding superior activity against HCT116 and MCF7 cells and better safety toward normal WI-38 cells than Staurosporine. The enzymatic assay revealed that3e,3d, and3ihad goodtubulin polymerization inhibition (IC 50  = 5.3, 8.6, and 8.05 µM, respectively) compared to the reference Combretastatin A4 (IC 50  = 2.15 µM). Moreover,3e,3l, and3fexhibited EGFR inhibition (IC 50  = 0.097, 0.154, and 0.334 µM, respectively) compared to Erlotinib (IC 50  = 0.056 µM). Compounds3eand3fwere investigated for their effects on the cell cycle, apoptosis induction, andwnt1/β-cateningene suppression. The apoptosis markers Bax, Bcl2, Casp3, Casp9, PARP1, and β-actin were detected by Western blot. In-silico molecular docking, physicochemical, and pharmacokinetic studies were implemented for the validation of dual mechanisms and other bioavailability standards. Hence, Compounds3eand3fare promising antiproliferative leads with tubulin polymerization and EGFR kinase inhibition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

Background/aim: This study aimed to investigate the effect of the new ciprofloxacin chalcone [7-(4-(N-substituted carbamoyl methyl) piperazin-1 yl)] on the proliferation, migration, and metastasis of MCF-7 and MDA-MB-231 breast cancer cell lines., Materials and Methods: Cell viability, colony formation and cell migration abilities were analysed. Cell cycle distribution and apoptosis were examined by flow cytometry. The molecular mechanism underlying chalcone's activity was investigated using qRT-PCR and western blotting., Results: This new ciprofloxacin chalcone significantly inhibited proliferation, colony formation, and cell migration abilities of both cancer cell lines. Furthermore, it initiated apoptosis and caused cell cycle arrest at G2/M and S phase in MCF-7 and MDA-MB-231 cell lines, respectively. In addition, it up-regulated the expression of pro-apoptotic factors, p53, PUMA and NOXA, and down-regulated the expression of anti-apoptotic factors, MDM2 and MDM4. At the same time, it inhibited epithelial-mesenchymal transition by increasing the expression of E-cadherin and decreasing the expression of TGF-β1, SNAI1, TWIST1, MMP2, and MMP9., Conclusion: This new ciprofloxacin chalcone exhibited promising apoptotic and anti-metastatic activities against MCF-7 and MDA-MB-231 breast cancer cell lines, and, therefore, is an attractive molecule for drug development in the treatment of breast cancer., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A group of novel chalcone derivatives comprising hydroxamic acid or 2-aminobenzamide group as zinc binding groups (ZBG) were synthesized. The structure of the prepared compounds was fully characterized by IR, NMR and elemental microanalyses. Most of the tested compounds displayed strong to moderate HDAC inhibitory activity. Some of these compounds showed potent anti-proliferative activity against human HepG2, MCF-7 and HCT-116 cell lines. In particular, compounds 4a and 4b exhibited significant anti-proliferative activity against the three cell lines compared to SAHA as reference drug and displayed promising profile as anti-tumor candidates. The results indicated that these chalcone derivatives could serve as a promising lead compounds for further optimization as antitumor agents., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A group of novel N-4-piperazinyl-ciprofloxacin-chalcone hybrids was prepared. One-dose anticancer test results indicated that compounds 3a and 3g exhibited the highest ability to inhibit the proliferation of different cancer cell lines. Compound 3a exhibited a broad-spectrum of anti-tumor activity without pronounced selectivity while compound 3g revealed high selectivity toward the leukemia subpanel with selectivity ratio of 6.71 at GI₅₀ level. Moreover, compounds 3e and 3j have shown remarkable topo II inhibitory activity compared to etoposide at 100 μM and 20 μM concentrations. Compounds 3e and 3j exhibited comparably potent topo I inhibitory activity at 20 μM concentration compared to camptothecin. Compounds 3e and 3j exhibited strong topo II inhibitory activities compared to topo I at 20 μM concentration. Studying of the solubility and partition coefficient revealed higher lipophilicity of the hybrids 3a-j compared to the parent ciprofloxacin., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

A group of nitric oxide (NO) donating chalcone derivatives was prepared by binding amino chalcones with different NO-donating moieties including; nitrate esters, oximes and furoxans. Screening of the anticancer activity of the target compounds revealed that the selected NO-donating compounds exhibited from mild to strong cytotoxic activity. The NO/chalcone hybrids 3a and 3b exhibited remarkable activity against different types of cancer cell lines especially against the colon and melanoma cancer cell lines. The nitrate ester 3a exhibited moderate selectivity toward colon cancer subpanel with selectivity ratio of 5.87 at TGI level., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

A group of novel nitric oxide (NO) donating chalcone derivatives was prepared by binding various amino chalcones with different NO donating moieties including; nitrate ester, oximes and furoxans. Most of the prepared compounds showed significant anti-inflammatory activity using carrageenan-induced rat paw edema method compared with indomethacin. The prepared compounds exhibited more protection than indomethacin in regard to gastric toxicity. Histopathological investigation confirmed the beneficial effects of the NO releasing compounds in reducing ulcer formation. The incorporation of the NO-donating group into the parent chalcone derivatives caused a moderate increase in the anti-inflammatory activity with a marked decrease in gastric ulcerations compared to their parent chalcone derivatives., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background/Aim: SARS‐CoV‐2 is one of the coronavirus families that emerged at the end of 2019. It infected the respiratory system and caused a pandemic worldwide. Fluoroquinolones (FQs) have been safely used as antibacterial agents for decades. The antiviral activity of FQs was observed. Moreover, substitution on the C‐7 position of ciprofloxacin enhanced its antiviral activity. Therefore, this study aims to investigate the antiviral activity of 7‐(4‐(N‐substituted‐carbamoyl‐methyl)piperazin‐1yl)‐chalcone in comparison with ciprofloxacin against SARS‐CoV‐2 main protease (Mpro). Materials and methods: Vero cells were infected with SARS‐CoV‐2. After treatment with ciprofloxacin and the chalcone at the concentrations of 1.6, 16, 160 nmol/L for 48 h, SARS‐CoV‐2 viral load was detected using real‐time qPCR, SARS‐CoV‐2 infectivity was determined using plaque assay, and the main protease enzyme activity was detected using in vitro 3CL‐protease inhibition assay. The activity of the chalcone was justified through molecular docking within SARS‐CoV‐2 Mpro, in comparison with ciprofloxacin. Results: The new chalcone significantly inhibited viral load replication where the EC50 was 3.93 nmol/L, the plaque formation ability of the virus was inhibited to 86.8% ± 2.47. The chalcone exhibited a significant inhibitory effect against SARS‐CoV‐2 Mpro in vitro in a dose‐dependent manner. The docking study into SARS‐CoV‐2 Mpro active site justified the importance of adding a substitution to the parent drug. Additionally, the assessment of the drug‐likeness properties indicated that the chalcone might have acceptable ADMET properties. Conclusion: The new chalcone might be useful and has new insights for the inhibition of SARS‐CoV‐2 Mpro. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Novel thienoquinoline-2-carboxamide-chalcone derivatives. • Structural elucidation. • Good Antiproliferaive Activity. • EGFR-kinase inhibition. • Molecular docking to ATP-binding and allosteric binding site. Abstract Novel thienoquinoline carboxamide-chalcone derivatives were prepared via the cyclization of acylated chalcones and 2-mercaptoquinoline-3-carbaldehyde in DMF with K 2 CO 3. Thienoquinolines 9a–f , h exhibited promising antiproliferative effect against all the tested cell lines and gave a significant activity as EGFR inhibitors, with IC 50 values ranging from 0.5 and 3.2 µM, and compounds 9e and 9f being the most active of the series. They also showed better activity than Erlotinib against melanoma cancer cell line A375. Moreover, compound 9f influenced pre G1 apoptosis and cell cycle arrest at G2/M phase. The binding mode of the best EGFR inhibitor 9e in the EGFR active site revealed that the thienoquinoline ring occupied the ATP-binding site while the chalcone moiety is located in the allosteric site and is responsible for the enhanced activity of these compounds. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two series of chalcones linked 1,2,4-oxadiazole 6a-f and their oxime 7a-f were designed and synthesized. • Compounds were evaluated for their in-vitro antimicrobial activity. • Compounds 6c , 7c , 7e and 7b proved to possess broad spectrum antibiotic activity against the Gram-positive and Gram-negative organism. • Compounds 6c , 7c , 7e and 7b with good inhibitory activity against E. coli gyrase. • The docking study revealed that compounds 6c and 7c fit into the DNA gyrase protein pocket and had good drug-likeness and acceptable physicochemical properties. New antibacterial drugs are urgently needed to tackle the rapid rise in multi-drug resistant bacteria. DNA gyrase is a validated target for the development of new antibacterial drugs. Thus, in the present investigation, a novel series of 1,2,4-oxadiazole-chalcone/oxime (6a-f) and (7a-f) were synthesized and characterized by IR, NMR (1H and 13C) and elemental analyses. The title compounds were evaluated for their in-vitro antimicrobial activity by the modified agar diffusion method as well as their E. coli DNA gyrase inhibitory activity. The minimum inhibitory concentration (MIC) and the structure activity relationships (SARs) were evaluated. Among all, compounds 6a , 6c-e , 7b and 7e were the most potent and proved to possess broad spectrum activity against the tested Gram-positive and Gram-negative organisms. Additionally, compounds 6a (against S. aureus) , 6c (against B. subtilis and E. hirae), 6e (against E. hirae), 6f , 7a and 7c (against E. coli) and 7d (against B. subtilis) , with MIC value of 3.12 μM were two-fold more potent than the standard ciprofloxacin (MIC = 6.25 μM). Mechanistically, compounds 6c , 7c , 7e and 7b had good inhibitory activity against E. coli gyrase with IC 50 values of 17.05, 13.4, 16.9, and 19.6 µM, respectively, in comparison with novobiocin (IC 50 = 12.3 µM) and ciprofloxacin (IC 50 = 10.5 µM). The molecular docking results at DNA gyrase active site revealed that the most potent compounds 6c and 7c have binding mode and docking scores comparable to that of ciprofloxacin and novobiocin suggesting their antibacterial activity via inhibition of DNA gyrase. Finally, the predicted parameters of Lipinski's rule of five and ADMET analysis showed that 6c and 7c had good drug-likeness and acceptable physicochemical properties. Therefore, the hybridization of the chalcone and oxadiazole moieties could be promising lead as antibacterial candidate which merit further future structural optimizations. [ABSTRACT FROM AUTHOR]

• Novel urea linked ciprofloxacin-chalcone hybrids 3a-j. • 3c and 3j showed remarkable cytotoxicity against HCT-116 and leukemia-SR cells. • Compounds 3c and 3j have inhibitory activity on both topoisomerases I/II and caspases-mediated apoptosis. • 3j induced cell cycle arrest at the G2/M phase, increased protein expression of Bax, and down-regulated the level of Bcl-2. A novel series of urea-linked ciprofloxacin (CP)-chalcone hybrids 3a-j were synthesized and screened by NCI-60 cancer cell lines as potential cytotoxic agents. Interestingly, compounds 3c and 3j showed remarkable antiproliferative activities against both colon HCT-116 and leukemia SR cancer cells compared to camptothecin, topotecan and staurosporine with IC 50 = 2.53, 2.01, 17.36, 12.23 and 3.1 μM for HCT-116 cells, respectively and IC 50 = 0.73, 0.64, 3.32, 13.72 and 1.17 μM for leukemia SR cells, respectively. Also, compounds 3c and 3j exhibited inhibitory activities against Topoisomerase (Topo) I with % inhibition = 51.19% and 56.72%, respectively, compared to camptothecin (% inhibition = 60.05%) and Topo IIβ with % inhibition = 60.81% and 60.06%, respectively, compared to topotecan (% inhibition = 71.09%). Furthermore, compound 3j arrested the cell cycle of leukemia SR cells at G2/M phase. It induced apoptosis both intrinsically and extrinsically via activation of proteolytic caspases cascade (caspases-3, −8, and −9), release of cytochrome C from mitochondria, upregulation of proapoptotic Bax and down-regulation of Bcl-2 protein level. Thus, the new ciprofloxacin derivative 3j could be considered as a potential lead for further optimization of antitumor agent against leukemia and colorectal carcinoma. [ABSTRACT FROM AUTHOR]