Synthesis, anticancer evaluation and molecular docking studies of new heterocycles linked to sulfonamide moiety as novel human topoisomerase types I and II poisons

Halawa, Ahmed H.; Elgammal, Walid E.; Hassan, Saber M.; Hassan, Ahmed H.E.; Nassar, Hesham S.; Ebrahim, Hassan Y.; Mehany, Ahmed B. M.; El‐Agrody, Ahmed M.

doi:10.1016/j.bioorg.2020.103725

Cited by 32 publications

(17 citation statements)

References 52 publications

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“…Notably, compound 18 was able to intercalate the DNA double helix similarly to that of the co‐crystallized inhibitor ( ASW ), which recommends it to be a potential DNA intercalator besides a promising topoisomerase II inhibitor as well, Table 3. Docking results of VEGFR2 and Topo II inhibition agreed with some previous studies [20,29] with the same target inhibition for benzene sulfonamide moieties, besides the experimental results of both targets′ inhibition of these newly synthesized derivatives.…”

Section: Resultssupporting

confidence: 88%

Design and Synthesis of Benzenesulfonamides Coupled with Piperidine, Morpholine, and N,N‐Dimethylethanamine Moieties as Apoptotic Inducers through VEGFR2 and Topoisomerase II Inhibition

Albujuq,

Althumayri,

Alharbi

et al. 2023

ChemistrySelect

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Novel hybrid series of benzenesulfonamide coupled with piperidine, morpholine, and N,N‐dimethylethanamine moieties at sulfonyl group were designed through pharmacophore hybridization, synthesized, and evaluated for cancer treatment. Benzenesulfonamide‐based derivatives had been synthesized, structurally elucidated, and biologically evaluated as potent VEGFR2 kinase and topoisomerase II inhibitors with cytotoxicity against MCF‐7 and HepG2 cells. Interestingly, the most cytotoxic compound against MCF‐7 and HepG2 cells exhibited promising IC50 values of 0.08 and 0.186 μM, respectively, compared to Doxorubicin as the reference drug with IC50 values of 7.67 and 8.28 μM. It exhibited promising dual enzyme inhibition VEGFR2 and Topoisomerase II with IC50 values of 13.24 nM and 8.3 μM compared to Sorafenib and Doxorubicin as standard drugs. It significantly stimulated total apoptotic breast cancer cell death by 55.25‐fold (34.26 % compared to 0.62 for the control), arresting the cell cycle at S‐phase, which affected the apoptosis‐mediated genes through upregulating P53, Bax, caspases 3, 8, and 9 and downregulating the anti‐apoptotic gene Bcl‐2. A molecular docking study was conducted to confirm the binding affinity of the designed compounds towards VEGFR2 and Topoisomerase II proteins with good binding energy and interactive modes as their co‐crystallized ligands.

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Section: Resultssupporting

confidence: 88%

Design and Synthesis of Benzenesulfonamides Coupled with Piperidine, Morpholine, and N,N‐Dimethylethanamine Moieties as Apoptotic Inducers through VEGFR2 and Topoisomerase II Inhibition

Albujuq,

Althumayri,

Alharbi

et al. 2023

ChemistrySelect

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“…The multidrug-resistant phenotype in cancer that mediates MDR also heavily relies on P-glycoprotein (P-gp/ABCB1) [29]. Based on our ongoing experiences to create effective anticancer benzochromenebased medicines, [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48], we have initiated the current study. Developing drugs with potential anti-proliferative activity against three cancer cell lines, PC-3, SKOV-3 and HeLa, while having no cytotoxic effect on normal cell lines HFL-1 and WI-38, was the main motivation behind our decision to design and synthesize β-enaminonitriles incorporating a 9-hydroxy-1H-benzo[f]chromene moiety.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 9-Hydroxy-1H-Benzo[f]chromene Derivatives with Effective Cytotoxic Activity on MCF7/ADR, P-Glycoprotein Inhibitors, Cell Cycle Arrest and Apoptosis Effects

Albalawi

El-Nassag

El-Eisawy

et al. 2022

IJMS

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β-Enaminonitriles bearing 9-hydroxy-1H-benzo[f]chromene moiety was synthesized. The targeted compounds were evaluated for their anti-proliferative activity against three human tumor cell lines, PC-3, SKOV-3 and HeLa, and the active cytotoxic compounds were further evaluated against cancer cells, MCF-7/ADR, and two normal cell lines, HFL-1 and WI-38. Few compounds were assigned to be the most potent derivatives against PC-3, SKOV-3 and HeLa cell lines in comparison with Vinblastine and Doxorubicin. Several compounds possessed a relatively good potency against MCF-7/ADR cells as compared with Doxorubicin and were tested as a P-gp inhibitor. Moreover, the halogenated substituents, 2,4-F2, 2,3-Cl2, 2,5-Cl2 and 3,4-Cl2; have good potency against P-gp-mediated MDR in MCF-7/ADR as compared with Doxorubicin. Meanwhile, Rho123 accumulation assays revealed that few compounds effectively inhibited P-pg and efflux function. In addition, certain derivatives induced apoptosis and an accumulation of the treated MCF-7/ADR cells in the G1, S and G1/S phases.

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“…In continuation of our efforts to discover oxygen-heterocyclic derivatives with promising antimicrobial and antitumor activities [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57], we present the synthesis of 3-amino-1-(4-chlorophenyl)-9-methoxy-1H-benzo[f ]chromene-2-carbonitrile and portray its crystallographic structure. Moreover, the antimicrobial behavior of the target molecule is evaluated and its minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentrations (MFC) are appraised.…”

Section: Introductionmentioning

confidence: 99%

The Crystal Structure of 3-Amino-1-(4-Chlorophenyl)-9-Methoxy-1H-Benzo[f]Chromene-2-Carbonitrile: Antimicrobial Activity and Docking Studies

et al. 2022

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Compound 3-amino-1-(4-chlorophenyl)-9-methoxy-1H-benzo[f]chromene-2-carbonitrile (4), was synthesized via the reaction of 7-methoxynaphthalen-2-ol (1), 4-chlorobenzaldehyde (2), and malononitrile (3) in an ethanolic piperidine solution under microwave irradiation. The synthesized pyran derivative 4 was asserted through spectral data and X-ray diffraction. The molecular structure of compound 4 was established unambiguously through the single crystal X-ray measurements and crystallized in the Triclinic, P-1, a = 8.7171 (4) Å, b = 10.9509 (5) Å, c = 19.5853 (9) Å, α = 78.249 (2)°, β = 89.000 (2)°, γ = 70.054 (2)°, V = 1717.88 (14) Å3, Z = 4. The target molecule has been screened for antibacterial and antifungal functionality. Compound 4 exhibited favorable antimicrobial activities that resembled the reference antimicrobial agents with an IZ range of 16–26 mm. In addition, MIC, MBC, and MFC were assessed and screened for molecule 4, revealing bactericidal and fungicidal effects. Lastly, a molecular docking analysis was addressed and conducted for this desired molecule.

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Synthesis, anticancer evaluation and molecular docking studies of new heterocycles linked to sulfonamide moiety as novel human topoisomerase types I and II poisons

Cited by 32 publications

References 52 publications

Design and Synthesis of Benzenesulfonamides Coupled with Piperidine, Morpholine, and N,N‐Dimethylethanamine Moieties as Apoptotic Inducers through VEGFR2 and Topoisomerase II Inhibition

Design and Synthesis of Benzenesulfonamides Coupled with Piperidine, Morpholine, and N,N‐Dimethylethanamine Moieties as Apoptotic Inducers through VEGFR2 and Topoisomerase II Inhibition

Synthesis of 9-Hydroxy-1H-Benzo[f]chromene Derivatives with Effective Cytotoxic Activity on MCF7/ADR, P-Glycoprotein Inhibitors, Cell Cycle Arrest and Apoptosis Effects

The Crystal Structure of 3-Amino-1-(4-Chlorophenyl)-9-Methoxy-1H-Benzo[f]Chromene-2-Carbonitrile: Antimicrobial Activity and Docking Studies

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