Synthesis and Biological Activity Evaluation of Coumarin-3-Carboxamide Derivatives

A series of novel coumarin-3-carboxamide derivatives were designed and synthesized to evaluate their biological activities. The compounds showed little to no activity against gram-positive and gram-negative bacteria but specifically showed potential to inhibit the growth of cancer cells. In particular, among the tested compounds, 4-fluoro and 2,5-difluoro benzamide derivatives (14b and 14e, respectively) were found to be the most potent derivatives against HepG2 cancer cell lines (IC50 = 2.62–4.85 μM) and HeLa cancer cell lines (IC50 = 0.39–0.75 μM). The activities of these two compounds were comparable to that of the positive control doxorubicin; especially, 4-flurobenzamide derivative (14b) exhibited low cytotoxic activity against LLC-MK2 normal cell lines, with IC50 more than 100 μM. The molecular docking study of the synthesized compounds revealed the binding to the active site of the CK2 enzyme, indicating that the presence of the benzamide functionality is an important feature for anticancer activity.

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Synthesis of N-Substituted Benzamide Derivatives and their Evaluation as Antitumor Agents

Medicinal Chemistry ◽

10.2174/1573406415666190712120611 ◽

2020 ◽

Vol 16 (4) ◽

pp. 555-562

Author(s):

Taiping Chen ◽

Hongwu Jiang ◽

Jianjun Zhou ◽

Zicheng Li ◽

Wencai Huang ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Antitumor Agents ◽

Cancer Cell Lines ◽

Zinc Ion ◽

Molecular Docking Study ◽

Chemical Structures ◽

Substituted Benzamide ◽

Benzamide Derivatives ◽

Antiproliferative Activities

Background: Histone deacetylases inhibitors (HDACIs) with different chemical structures have been reported to play an important role in the treatment of cancer. Objective: The study aims to modify the structure of Entinostat (MS-275) to discover new compounds with improved anti-proliferative activities and perform SAR studies on this class of bioactive compounds. Methods: Fourteen N-substituted benzamide derivatives were synthesized and their antiproliferative activities were tested with four cancer cell lines (MCF-7, A549, K562 and MDA-MB- 231) by MTT assay. Results: Compared with MS-275, six compounds exhibited comparable or even better antiproliferative activities against specific/certain cancer cell lines. Conclusion: The preliminary SARs showed that (ⅰ) the 2-substituent of the phenyl ring in the R group and heteroatoms of amide which can chelate with zinc ion are critical to the antiproliferative activity and (ⅱ) chlorine atom or nitro-group on the same benzene ring largely decreases their anti-proliferative activity. Molecular docking study illustrated the interaction (binding affinity) between the synthesized compounds and HDAC2 was observed to be similar to that of MS-275.

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Anticariogenic And Anticarcinogenic Effects Of Garcinia Mangostana Pericarp Extracts On Cariogenic Bacteria And On Cancer Cell Lines With Molecular Docking Study

International Journal of Pharmaceutical Research ◽

10.31838/ijpr/2021.13.02.040 ◽

2021 ◽

Vol 13 (02) ◽

Keyword(s):

Molecular Docking ◽

Cell Lines ◽

Cancer Cell ◽

Docking Study ◽

Cancer Cell Lines ◽

Garcinia Mangostana ◽

Molecular Docking Study ◽

Cariogenic Bacteria

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EV Targeting MCF-7 Breast Cancer Cell Lines Inhibit Both mTOR and HIF-1A: Molecular Docking Study

Medico-Legal Update ◽

10.37506/mlu.v21i1.2511 ◽

2021 ◽

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Docking Study ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Molecular Docking Study ◽

Mcf 7

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Synthesis, Molecular Docking Screening and Anti-Proliferative Potency Evaluation of Some New Imidazo[2,1-b]Thiazole Linked Thiadiazole Conjugates

Molecules ◽

10.3390/molecules25214997 ◽

2020 ◽

Vol 25 (21) ◽

pp. 4997

Author(s):

Huda R. M. Rashdan ◽

Aboubakr H. Abdelmonsef ◽

Ihsan A. Shehadi ◽

Sobhi M. Gomha ◽

Abdel Mohsen M. Soliman ◽

...

Keyword(s):

Molecular Docking ◽

Cell Lines ◽

Cancer Cell ◽

Docking Study ◽

Cancer Cell Lines ◽

Hepatic Cancer ◽

Molecular Docking Study ◽

Drug Candidates ◽

Ft Ir ◽

Thiadiazole Derivatives

Background: Imidazo[2,1-b]thiazole scaffolds were reported to possess various pharmaceutical activities. Results: The novel compound named methyl-2-(1-(3-methyl-6-(p-tolyl)imidazo[2,1-b]thiazol-2-yl)ethylidene)hydrazine-1-carbodithioate 3 acted as a predecessor molecule for the synthesis of new thiadiazole derivatives incorporating imidazo[2,1-b]thiazole moiety. The reaction of 3 with the appropriate hydrazonoyl halide derivatives 4a–j and 7–9 had produced the respective 1,3,4-thiadiazole derivatives 6a–j and 10–12. The chemical composition of all the newly synthesized derivatives were confirmed by their microanalytical and spectral data (FT-IR, mass spectrometry, 1H-NMR and 13C-NMR). All the produced novel compounds were screened for their anti-proliferative efficacy on hepatic cancer cell lines (HepG2). In addition, a computational molecular docking study was carried out to determine the ability of the synthesized thiadiazole molecules to interact with active site of the target Glypican-3 protein (GPC-3). Moreover, the physiochemical properties of the synthesized compounds were derived to determine the viability of the compounds as drug candidates for hepatic cancer. Conclusion: All the tested compounds had exhibited good anti-proliferative efficacy against hepatic cancer cell lines. In addition, the molecular docking results showed strong binding interactions of the synthesized compounds with the target GPC-3 protein with lower energy scores. Thus, such novel compounds may act as promising candidates as drugs against hepatocellular carcinoma.

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Wogonoside: Anti-human colon cancer activities and survey of HMG-CoA ‎reductase inhibition properties with molecular modeling

Archives of Medical Science ◽

10.5114/aoms/143792 ◽

2021 ◽

Author(s):

Jiamiao Liu ◽

Huifang Tan ◽

Qing Zeng

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Catalytic Domain ◽

Biological Activities ◽

Cancer Cell Lines ◽

Dependent Manner ◽

Molecular Docking Study ◽

Human Colon Cancer ◽

Hmg Coa Reductase ◽

Coa Reductase

IntroductionThe biological activities and interactions of wogonoside in the presence of HMG-COA reductase were investigated using the molecular docking study as a versatile theoretical approach. Wogonoside showed a considerable binding affinity to the enzyme with a docking score of -7.582 kcal/mol.Material and methodsThe in vitro cytotoxic and anti- colon ‎ carcinoma effects of biologically synthesized Wogonoside ‎against GP5d, MDST8‎, HCA-46‎, HT115, LS174T, and COLO 320DM cancer cell lines were ‎assessed.ResultsThe results indicated that the compound makes hydrophobic contacts with essential residues of the catalytic domain of the enzyme. Therefore, wogonosid could be considered as a potential inhibitor for HMG-COA reductase. The IC50 of the Wogonoside were 105, 198, 173, 382, 71, and 183 µg/mL against GP5d, ‎MDST8‎, HCA-46‎, HT115, LS174T, and COLO 320DM cancer cell lines. The anti-colon‎ ‎carcinoma properties of the Wogonoside could significantly remove GP5d, MDST8‎, HCA-46‎, ‎HT115, LS174T, and COLO 320DM cancer cell lines in a time and concentration-dependent ‎manner by MTT assay. ‎ConclusionsIt appears that the anti-human colorectal carcinoma effect of recent nanoparticles is due to their antioxidant effects. We have obtained results for the HMG-CoA Reductase enzyme at the micromolar level. In our study, inhibition result of on HMG-CoA reductase showed lower values 28.70±4.73 micromolar.

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Naphthoquinone-based hydrazone hybrids: synthesis and potent activity against cancer cell lines

Medicinal Chemistry ◽

10.2174/1573406416666200817164308 ◽

2020 ◽

Vol 16 ◽

Author(s):

Délis Galvão Guimarães ◽

Arlan de Assis Gonsalves ◽

Larissa Araújo Rolim ◽

Edigênia Cavalcante Araújo ◽

Victória Laysna dos Anjos Santos ◽

...

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Cancer Cell ◽

Biological Activities ◽

Supporting Electrolyte ◽

Cancer Cell Lines ◽

Molecular Structures ◽

Cytotoxic Activities ◽

Electrochemical Studies ◽

Ic50 Values

Background: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, then the modification at their redox center is an interesting strategy to overcome such harmful activity. Objective: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and β-lapachones (α and β, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. Method: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. Result: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, being compounds 3 and 4 the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than β-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90–12.40 μM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. Conclusion: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.

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Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

Molecules ◽

10.3390/molecules26133923 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3923

Author(s):

Adel A.-H. Abdel-Rahman ◽

Amira K. F. Shaban ◽

Ibrahim F. Nassar ◽

Dina S. EL-Kady ◽

Nasser S. M. Ismail ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Molecular Docking Study ◽

Human Cancer Cell Lines ◽

Hct 116 ◽

Mcf 7

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

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Synthesis and Biological Activities of Cyclodepsipeptides of Aurilide Family from Marine Origin

Marine Drugs ◽

10.3390/md19020055 ◽

2021 ◽

Vol 19 (2) ◽

pp. 55

Author(s):

Synthia Michon ◽

Florine Cavelier ◽

Xavier J. Salom-Roig

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Biological Activities ◽

Natural Compounds ◽

Cancer Cell Lines ◽

Hydroxy Ester ◽

Marine Cyanobacteria ◽

Synthetic Analogues ◽

Marine Origin ◽

Total Syntheses

Aurilides are a class of depsipeptides occurring mainly in marine cyanobacteria. Members of the aurilide family have shown to exhibit strong cytotoxicity against various cancer cell lines. These compounds bear a pentapeptide, a polyketide, and an α-hydroxy ester subunit in their structure. A large number of remarkable studies on aurilides have emerged since 1996. This comprehensive account summarizes the biological activities and total syntheses of natural compounds of the aurilide family as well as their synthetic analogues.

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Synthesis of Lapachol-Based Glycosides and Glycosyl Triazoles with Antiproliferative Activity Against Several Cancer Cell Lines

10.21203/rs.3.rs-916974/v1 ◽

2021 ◽

Author(s):

Flaviano Melo Ottoni ◽

Lucas Bonfim Marques ◽

Juliana Martins Ribeiro ◽

Lucas Lopardi Franco ◽

José Dias Souza Filho ◽

...

Keyword(s):

Antitumor Activity ◽

Adverse Effects ◽

Dna Fragmentation ◽

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Biological Activities ◽

Cancer Cell Lines ◽

Tumor Cell Lines

Abstract Lapachol (1), a natural naphthoquinone, presents several biological activities including antitumor activity, used as anticancer coadjuvant whose use was abandoned because of adverse effects. Herein, we reported the synthesis and cytotoxicity evaluation against cancer cell lines of a series of Oglycosides and glycosyl triazoles derived from lapachol. In addition to the determination of IC50, the DNA fragmentation and clonogenicity were also evaluated. The glycoside derived from D-glucose (5) was far more active than lapachol (1) and more active in tumor cell lines HL60, Jurkat, THP-1 and MDA-MB-231 than to the non-tumoral PBMC cell line, indicating an improvement in activity and selectivity as compared with lapachol (1). Compound 5 and the glycosides derived from D-galactose (14), D-N-acetylglucosamine (15) and L-fucose (16) showed good results in the DNA fragmentation and clonogenicity assays in the studies of subdiploid DNA content, indicating a pro-apoptotic potential and a good antiproliferative activity of these glycosides.

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