Anticancer Activity of a scarcely investigated Red Sea Brown Alga Hormophysa cuneiformis against HL60, A549, HCT116 and B16 Cell Lines

Background: In spite of current progress in treatment methods, cancer is a major source of morbidity and death rate all over the world. Traditional chemotherapeutic agents aim to divide cancerous cells, are often associated with deleterious side effects to healthy cells and tissues. Host defense peptides Cecropin A and B obtained from insects are capable to lyses various types of human cancer cells at peptide concentrations which are not fatal to normal eukaryotic cells. Methods: In the present work we have designed short chain α-helical linear and cyclic peptide from cecropin A having same cationic charge, hydrophobicity and helicity. Synthesis of designed novel short chain linear (10) and cyclic compound (12) was accomplished by using solution phase method. All the coupling reactions were carried out by using dicyclohexylcarbodiimide (DCC) as the coupling reagent at room temperature in the presence of N-methylmorpholine (NMM) as the base. The Structure of newly synthesized peptidse were elucidated by 1H-NMR, 13C-NMR, FT-IR, FABMS and elemental analysis data.Cytotoxicity of synthesized compound was tested against Dalton’s Lymphoma Ascites (DLA), Ehrlich’s Ascites Carcinoma (EAC) and MCF-7 cell lines by using MTT assay and 5-FU as reference compound. Results: From biological assessment,it was found that short chain cyclicpeptide12 showed high level of cytotoxic activity against DLA and EAC cell lines. Conclusion: By utilizing a structure-based rational approach to anticancer peptide design from cecropin A, we were able to develop short chain linear and cyclic peptides having same charge, hydrophobicity and with improved activity. Systematically removing amino acids, we were able to retaining peptide charge and hydrophobicity/hydrophilicity in linear and cyclic peptide which results to optimize the anticancer activity against DLA and EAC cell lines.

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Extraction, Chemical Composition, Antioxidant Property and In vitro Anticancer Activity of Silymarin from Silybum Marianum On Kb and A549 Cell Lines

Current Drug Discovery Technologies ◽

10.2174/1570163817666200827111127 ◽

2020 ◽

Vol 17 ◽

Author(s):

Mojgan Azadpour ◽

Mohammad Mehdi Farajollahi ◽

Ali Mohammad Varzi ◽

Pejman Hashemzadeh ◽

Hossein Mahmoudvand ◽

...

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

A549 Cell ◽

Hplc Analysis ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Antioxidant Property ◽

Silybum Marianum ◽

Stable Free Radical

Introduction: This study aimed to evaluate the antioxidant property of silymarin (SM) extracted from the seed of Silybum marianum and its anticancer activity on KB and A549 cell lines following 24, 48, and 72 h of treatment. Methods: Ten grams of powdered S. marianum seeds were defatted using n-hexane for 6 hours and then extracted by methanol. The silymarin extracted of extraction components The extracted components of silymarin were measured by spectrophotometric assay and HPLC analysis. 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, phenol content, total flavonoid content, and total antioxidant capacity were measured to detect the antioxidant properties of SM. The anticancer activity of the SM on cell lines evaluated by MTT. Results: In HPLC analysis, more than 50% of the peaks were related to silibin A and B. SM was reducedDPPH (the stable free radical) with a 50% inhibitory concentration (IC50) of 6.56 μg/ ml in comparison with butylated hydroxyl toluene (BHT), which indicated an IC50 of ~3.9 μg/ ml.The cytotoxicity effect of SM on the cell lines was studied by MTT assay. The cytotoxicity effect of the extracted silymarin on KB and A549 cell lines was observed up to 80 and 70% at 156 and 78 µg/ml, respectively. The IC50 value of the extracted SM on KB and A549 cell lines after 24 hours of treatment was seen at 555 and 511 µg/ml, respectively. Conclusion: Due to the good antioxidant and anticancer properties of the isolated silymarin, its use as an anticancer drug is suggested.

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Design, Synthesis and Biological Evaluation of 3-(3,4,5-Trimethoxyphenyl)- 5-(2-(5-arylbenzo[b]thiophen-3-yl)oxazol-5-yl)isoxazole Derivatives as Anticancer Agents

Letters in Organic Chemistry ◽

10.2174/1570178616666191004105445 ◽

2020 ◽

Vol 17 (5) ◽

pp. 345-351

Author(s):

Syndla Premalatha ◽

G. Rambabu ◽

Islavathu Hatti ◽

Dittakavi Ramachandran

Keyword(s):

Breast Cancer ◽

Anticancer Activity ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Biological Evaluation ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Isoxazole Derivatives

A new series of 3-(3,4,5-trimethoxyphenyl)-5-(2-(5-arylbenzo[b]thiophen-3-yl)oxa zol-5- yl)isoxazole derivatives were designed and synthesized. All these derivatives were evaluated for their anticancer activity against various human cancer cell lines such as MCF-7 (breast cancer), A549 (lung cancer), DU-145 (prostate cancer) and MDA MB-231 (breast cancer)-four human cancer cell lines by using MTT assay. Here, etoposide was used as a standard reference drug and most of the compounds were exhibited good anticancer activity with respect to cell lines. Among all compounds, five compounds 11b, 11c, 11f, 11i and 11j showed more potent activity than standard drug, in which, compound 11f was the most promising compound.

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Isolation of New Glycosides from Anemarrhena Asphodeloides Rhizome and Screening of their Anticancer Activity

Letters in Organic Chemistry ◽

10.2174/1570178615666181102125553 ◽

2019 ◽

Vol 16 (6) ◽

pp. 474-477 ◽

Cited By ~ 1

Author(s):

Pham Van Khang ◽

Nguyen Thi Hien Lan ◽

Le Quang Truong ◽

Mai Thi Minh Chau ◽

Mai Xuan Truong ◽

...

Keyword(s):

Anticancer Activity ◽

Spectral Data ◽

Cell Lines ◽

Cancer Cell ◽

Spectroscopic Analysis ◽

2D Nmr ◽

Ic50 Values ◽

Nmr Techniques ◽

Inhibitory Activities ◽

Anemarrhena Asphodeloides

In this report, two new steroidal glycosides were isolated and determined from n-butanol fraction of A.asphodeloides. The structures were confirmed in comparison with the spectral data of known compounds by using different spectroscopic analysis approaches including 1D & 2D-NMR techniques and HRMS. The anti-proliferation screening against cancer cell lines A549 and HeLa indicated that compound 1 exhibited good inhibitory activities with IC50 values of 0.79 and 0.55 µg/mL, respectively.

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Arylhydrazono/Aryldiazenyl Pyrazoles: Green One-Pot Solvent-Free Synthesis and Anticancer Evaluation

Letters in Organic Chemistry ◽

10.2174/1570178617666200320104923 ◽

2020 ◽

Vol 17 (10) ◽

pp. 772-778

Author(s):

Abdulrhman Alsayari ◽

Abdullatif Bin Muhsinah ◽

Yahya I. Asiri ◽

Jaber Abdullah Alshehri ◽

Yahia N. Mabkhot ◽

...

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Anticancer Agents ◽

Binding Mode ◽

Docking Studies ◽

Solvent Free ◽

Pyrazole Derivatives ◽

One Pot ◽

Solvent Free Conditions ◽

Hybrid Molecules

The aim of this study was to synthesize and evaluate the biological activity of pyrazole derivatives, in particular, to perform a “greener” one-pot synthesis using a solvent-free method as an alternative strategy for synthesizing hydrazono/diazenyl-pyridine-pyrazole hybrid molecules with potential anticancer activity. Effective treatment for all types of cancers is still a long way in the future due to the severe adverse drug reactions and drug resistance associated with current drugs. Therefore, there is a pressing need to develop safer and more effective anticancer agents. In this context, some hybrid analogues containing the bioactive pharmacophores viz. pyrazole, pyridine, and diazo scaffolds were synthesized by one-pot method. Herein, we describe the expedient synthesis of pyrazoles by a onepot three-component condensation of ethyl acetoacetate/acetylacetone, isoniazid, and arenediazonium salts under solvent-free conditions, and the evaluation of their cytotoxicity using a sulforhodamine B assay on three cancer cell lines. Molecular docking studies employing tyrosine kinase were also carried out to evaluate the binding mode of the pyrazole derivatives under study. 1-(4-Pyridinylcarbonyl)-3- methyl-4-(2-arylhydrazono)-2-pyrazolin-5-ones and [4-(2-aryldiazenyl)-3,5-dimethyl-1H-pyrazol-1- yl]-4-pyridinylmethanones, previously described, were prepared using an improved procedure. Among these ten products, 1-isonicotinoyl-3-methyl-4-[2-(4-nitrophenyl)hydrazono]-2-pyrazolin-5-one (1f) displayed promising anticancer activity against the MCF-7, HepG2 and HCT-116 cell lines, with an IC50 value in the range of 0.2-3.4 μM. In summary, our findings suggest that pyrazoles containing hydrazono/ diazenyl and pyridine pharmacophores constitute promising scaffolds for the development of new anticancer agents.

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(Substituted)-benzo[b]thiophene-4-carboxamide Synthesis and Antiproliferative Activity Study

Letters in Drug Design & Discovery ◽

10.2174/1570180815666181004114125 ◽

2020 ◽

Vol 17 (5) ◽

pp. 563-573 ◽

Cited By ~ 2

Author(s):

Chandrakant Dhondiram Pawar ◽

Dattatraya Navnath Pansare ◽

Devanand Baburao Shinde

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Proliferative Activity ◽

Thiophene Ring ◽

Amide Group ◽

Peptide Coupling ◽

Ic50 Value ◽

Important Building Block ◽

Mcf 7

Background: Thiophene ring forms important building block in medicinal chemistry. Literature reveals that thiophene ring in combination with different groups shows different activity. By keeping these things in mind we have designed and synthesized a new series of amide and sulfonamide coupled thiophene. A series of novel substituted 3-sulfamoylbenzo[b]thiophene-4- carboxamide molecules containing sulfonamide and amide group were designed, synthesized and used for anti-proliferative activity study. Methods: The final compounds 16-36 were synthesized by using series of reactions comprising sulfonation, sulfonamide coupling, hydrolysis and peptide coupling. The yields of compounds 16- 36 are in the range of 90-98%. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR, LCMS and the purity was checked through HPLC analysis. The compounds were further tested for their in vitro anticancer activity against a series of cell lines A549, HeLa, MCF-7 and Du-145. Results: The intermediates 8-13, 15 and final compounds 16-36 were synthesized in good yields. The synthesized compounds were further tested for their anticancer activity and most of compounds showed moderate to good anticancer activity against all four cell lines. Conclusion: We have synthesized 21 compounds and were screened for anticancer activity against MCF-7, HeLa, A-549 and Du-145 cancer cell lines. Most of the compounds were active for tested cell lines with IC50 value in the range of 1.81 to 9.73 μM. The compounds 18, 19, 21, 25, 30, 31 and 33 are most active in cell line data with IC50 value in the range of 1.81 to 2.52 μM.

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Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with ω-Hydroxylalkylamine Side-Chains of Different Lengths

Medicinal Chemistry ◽

10.2174/1573406414666180912105851 ◽

2019 ◽

Vol 15 (5) ◽

pp. 550-560

Author(s):

Mateusz D. Tomczyk ◽

Anna Byczek-Wyrostek ◽

Klaudia Strama ◽

Martyna Wawszków ◽

Przemysław Kasprzycki ◽

...

Keyword(s):

Anticancer Activity ◽

Cancer Cells ◽

Cell Lines ◽

Inhibitory Activity ◽

Topoisomerase Ii ◽

Significant Activity ◽

Anticancer Activities ◽

Human Colon Cancer ◽

Substitution Pattern ◽

Topo Ii

Background: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. Objective: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. Methods: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. Results: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. Conclusion: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.

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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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Synthesis and Anticancer Activity of 9-O-Pyrazole Alkyl Substituted Berberine Derivatives

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180717121208 ◽

2019 ◽

Vol 18 (11) ◽

pp. 1639-1648 ◽

Cited By ~ 5

Author(s):

Daipeng Xiao ◽

Fen He ◽

Dongming Peng ◽

Min Zou ◽

Junying Peng ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Docking ◽

Anticancer Activity ◽

Cell Lines ◽

Human Lung Cancer ◽

Drug Candidate ◽

Molecular Docking Study ◽

Protective Function ◽

Anti Cancer ◽

Cancer Activity

Background: Berberine (BBR), an isoquinoline plant alkaloid isolated from plants such as Coptis chinensis and Hydrastis canadensis, own multiple pharmacological activities. Objective: In this study, seven BBR derivatives were synthesized and their anticancer activity against HeLa cervical and A549 human lung cancer cell lines were evaluated in vitro. Methods: The anti-cancer activity was measured by MTT assay, and apoptosis was demonstrated by the annexin V-FITC/PI staining assay. The intracellular oxidative stress was investigated through DCFH-DA assay. The molecular docking study was carried out in molecular operating environment (MOE). Results: Compound B3 and B5 showed enhanced anti-cancer activity compared with BBR, the IC50 for compound B3 and B5 were significantly lower than BBR, and compound B3 at the concentration of 64 or 128 µM induced apoptosis in HeLa and A549 cell lines. The reactive oxygen species (ROS) was generated in both cell lines when treated with 100 µM of all the compounds, and compound B3 and B5 induced higher activity in the generation of ROS, while compound B3 exhibited the highest activity, these results are in accordance with the cytotoxicity results, indicating the cytotoxicity were mostly generated from the oxidative stress. In addition, molecular docking analysis showed that compound B3 had the greatest affinity with Hsp90. Upon binding, the protective function of Hsp90 was lost, which might explain its higher cytotoxicity from molecular interaction aspect. Conclusion: All the results demonstrated that compound B3 and B5 showed significantly higher anti-cancer ability than BBR, and compound B3 is a promising anticancer drug candidate.

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