Docking studies, synthesis, characterization, and cytotoxicity activity of new bis-chalcones derivatives

Introduction: A bis-chalcones were prepared by the reaction of terephthalaldehyde with 3-acetyl-2,5-dichlorothiophene or 3-acetyl- 5-chlorothiophene and reaction cyclo ketone derivatives with phenyl aldehyde derivatives in good yields. Methods: The molecular docking studies were conducted using the Discovery Studio (DSv4.5) and MG. Tools installed in Window 10. The cancer receptor (3ERT) was downloaded from the protein data bank (PDB). All new compounds were characterized by IR, 1H-NMR, 13C-NMR, 2D-NMR, and CHN elemental analysis. The anticancer activity of the synthesized compounds was determined using MTT (3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) reduction assay against MCF-7 cells, and then the minimum inhibitory concentration (IC50) was determined with the reference of the standard drug tamoxifen. Results: The results showed that compound 6 showed more potent activity in inhibiting growth on both types of MCF-7 compared to reference tamoxifen.

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Synthesis and Anti-Proliferative Assessment of Triazolo-Thiadiazepine and Triazolo-Thiadiazine Scaffolds

Molecules ◽

10.3390/molecules24244471 ◽

2019 ◽

Vol 24 (24) ◽

pp. 4471 ◽

Cited By ~ 8

Author(s):

Ahmed T. A. Boraei ◽

Hazem A. Ghabbour ◽

Mohamed S. Gomaa ◽

El Sayed H. El Ashry ◽

Assem Barakat

Keyword(s):

Single Crystal ◽

Cell Lines ◽

Cancer Cell ◽

2D Nmr ◽

Cancer Cell Lines ◽

Docking Studies ◽

X Ray ◽

Cytotoxicity Activity ◽

Human Liver Cancer ◽

Mcf 7

A series of triazolo-thiadiazepines 4a–k were synthesized with excellent yields using dehydrated PTSA as a catalyst in toluene. Two triazolo-thiadiazines were obtained; 8a was formed directly by reflux in ethanol, whereas, PTSA promoted the formation of 8b. The molecular structure of the formed triazolo-thiadiazepines is identical to the imine-form 4a–k and not the enamine-tautomer 6a–k. The structures of the newly synthesized triazolo-thiadiazepines 4a–k and triazolo-thiadiazines 8a–b were elucidated using NMR (1H, and 13C), 2D NMR, HRMS, and X-ray single crystal. Furthermore, 4a was deduced using X-ray single crystal diffraction analysis. These new thiadiazepine hits represent an optimized series of previously synthesized indole-triazole derivatives for the inhibition of EGFR. The cytotoxicity activity against two cancer cell lines including human liver cancer (HEPG-2) and breast cancer (MCF-7) was promising, with IC50 between 12.9 to 44.6 µg/mL and 14.7 to 48.7 µg/mL for the tested cancer cell lines respectively, compared to doxorubicin (IC50 4.0 µg/mL). Docking studies revealed that the thiadiazepine scaffold presented a suitable anchor, allowing good interaction of the various binding groups with the enzyme binding regions and sub-pockets.

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Synthesis, Biological Activities and Docking Studies of Novel 4-(Arylaminomethyl)benzamide Derivatives as Potential Tyrosine Kinase Inhibitors

Molecules ◽

10.3390/molecules24193543 ◽

2019 ◽

Vol 24 (19) ◽

pp. 3543

Author(s):

Elena Kalinichenko ◽

Aliaksandr Faryna ◽

Viktoria Kondrateva ◽

Alena Vlasova ◽

Valentina Shevchenko ◽

...

Keyword(s):

Anticancer Agents ◽

Tyrosine Kinases ◽

Kinase Inhibitors ◽

Biological Activities ◽

Data Bank ◽

Docking Studies ◽

Cytotoxicity Activity ◽

Her 2 ◽

Solid Cell ◽

New Compounds

A number of new compounds containing the 4-(aminomethyl)benzamide fragment as a linker were designed and synthesized, and their biological activities were evaluated as potential anticancer agents. The cytotoxicity activity of the designed compounds was studied in two hematological and five solid cell lines in comparison with the reference drugs. Targeted structures against eight receptor tyrosine kinases including EGFR, HER-2, HER-4, IGF1R, InsR, KDR, PDGFRa, and PDGFRb were investigated. The majority of the compounds showed a potent inhibitory activity against the tested kinases. The analogues 11 and 13 with the (trifluoromethyl)benzene ring in the amide or amine moiety of the molecule were proven to be highly potent against EGFR, with 91% and 92% inhibition at 10 nM, respectively. The docking of synthesized target compounds for nine protein kinases contained in the Protein Data Bank (PDB) database was carried out. The molecular modeling results for analogue 10 showed that the use of the 4-(aminomethyl)benzamide as a flexible linker leads to a favorable overall geometry of the molecule, which allows one to bypass the bulk isoleucine residue and provides the necessary binding to the active center of the T315I-mutant Abl (PDB: 3QRJ).

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Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors

Zeitschrift für Naturforschung C ◽

10.1515/znc-2020-0104 ◽

2020 ◽

Vol 75 (9-10) ◽

pp. 353-362

Author(s):

Begüm Nurpelin Sağlık ◽

Ahmet Mücahit Şen ◽

Asaf Evrim Evren ◽

Ulviye Acar Çevik ◽

Derya Osmaniye ◽

...

Keyword(s):

Anticancer Activity ◽

In Silico ◽

Biological Effects ◽

Docking Studies ◽

Benzimidazole Derivatives ◽

Binding Modes ◽

Reference Drug ◽

In Silico Studies ◽

New Compounds ◽

Mcf 7

AbstractInhibition of aromatase enzymes is very important in the prevention of estrogen-related diseases and the regulation of estrogen levels. Aromatase enzyme is involved in the final stage of the biosynthesis of estrogen, in the conversion of androgens to estrogen. The development of new compounds for the inhibition of aromatase enzymes is an important area for medicinal chemists in this respect. In the present study, new benzimidazole derivatives have been designed and synthesized which have reported anticancer activity in the literature. Their anticancer activity was evaluated against human A549 and MCF-7 cell lines by MTT assay. In the series, concerning MCF-7 cell line, the most potent compounds were the 4-benzylpiperidine derivatives 2c, 2g, and 2k with IC50 values of 0.032 ± 0.001, 0.024 ± 0.001, and 0.035 ± 0.001 µM, respectively, compared to the reference drug cisplatin (IC50 = 0.021 ± 0.001 µM). Then, these compounds were subject to further in silico aromatase enzyme inhibition assays to determine the possible binding modes and interactions underlying their activity. Thanks to molecular docking studies, the effectiveness of these compounds against aromatase enzyme could be simulated. Consequently, it has been found that these compounds can be settled very properly to the active site of the aromatase enzyme.

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Halo-phenolic metabolites and their in vitro antioxidant and cytotoxic activities from the Red Sea alga Avrainvillea amadelpha

Zeitschrift für Naturforschung C ◽

10.1515/znc-2020-0221 ◽

2021 ◽

Vol 76 (5-6) ◽

pp. 213-218

Author(s):

Usama W. Hawas ◽

Lamia T. Abou El-Kassem ◽

Radwan Al-farawati ◽

Fekri M. Shaher

Keyword(s):

2D Nmr ◽

Cytotoxic Activities ◽

Dpph Radical ◽

Srb Assay ◽

Phenolic Metabolites ◽

2D Nmr Spectra ◽

New Compounds ◽

Benzaldehyde Derivatives ◽

Mcf 7

Abstract From the green alga Avrainvillea amadelpha, two new naturally halo-benzaldehyde derivatives were isolated by various chromatographic methods along with 10 known metabolites of bromophenols, sulfonoglycolipid, and steroids. Based on the 1D and 2D NMR spectra as well as on MS data, the structures of the new compounds were identified as 5-bromo-2-(3-bromo-4-hydroxybenzyl)-3,4-dihydroxybenzaldehyde named avrainvilleal (1), and 3-iodo-4-hydroxy-benzaldehyde (2). Using SRB assay, both compounds showed mild and weak cytotoxic activity against HeLa and MCF-7 cancer cell lines, compared to the good activity of their extract (IC50 values 3.1 and 4.3 μg/mL, respectively). However, avrainvilleal (1) displayed an effective scavenged DPPH radical activity with IC50 value 3.5 μM, compared to the antioxidant quercetin with IC50 value 1.5 μM.

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Molecular modelling, synthesis and antitumour activity of carbocyclic analogues of netropsin and distamycin--new carriers of alkylating elements.

Acta Biochimica Polonica ◽

10.18388/abp.2000_4059 ◽

2000 ◽

Vol 47 (1) ◽

pp. 23-35 ◽

Cited By ~ 12

Author(s):

D Bartulewic ◽

A Markowska ◽

S Wołczyński ◽

M Dabrowska ◽

A Rózański

Keyword(s):

Molecular Modelling ◽

Methoxy Group ◽

Antitumour Activity ◽

National Laboratory ◽

Data Bank ◽

Brookhaven National Laboratory ◽

Ortho Position ◽

Standard Cell ◽

New Compounds ◽

Mcf 7

A series of netropsin and distamycin analogues was synthesised and investigated by molecular modelling. The lowest-energy conformations of four carbocyclic lexitropsins, potential carriers of alkylating elements, were obtained using the HyperChem 4.0 program, and compared with the DNA-lexitropsin crystal structures from the Brookhaven National Laboratory Protein Data Bank. A method for synthesis of carbocyclic lexitropsins was elaborated, with the use of a nitro group or azobenzene as precursors for the aromatic amino group. The influence of methoxy group in ortho position with respect to amide groups on the activity of the new compounds was investigated. All of the compounds tested showed high antitumour activity in the standard cell line of mammalian tumour MCF-7.

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Synthesis, Characterization and Anticancer Evaluation of Nitrogen Substituted 1-(3-Aminoprop-1-ynyl)-4-Hydroxyanthraquinone Derivatives

10.21203/rs.3.rs-306809/v1 ◽

2021 ◽

Author(s):

Nafisa S. Sirazhetdinova ◽

Dmitry S Baev ◽

Victor A. Savelyev ◽

Tatyana S. Golubeva ◽

Lyubov S. Klimenko ◽

...

Keyword(s):

Cancer Cells ◽

Sonogashira Reaction ◽

Secondary Amines ◽

One Pot ◽

Standard Drug ◽

Three Component Reaction ◽

G Quadruplex ◽

New Compounds ◽

Substituted 1 ◽

Mcf 7

Abstract Anthraquinones are of significant interest due to their biological activity, coloring properties and synthetic applications. Here, we describe a mild and convenient method for modification of 1-ethynyl-4-hydroxyanthraquinone that was obtained from the Sonogashira reaction of 1-hydroxy-4-iodoanthraquinone with alkynes. The copper(I) catalyzed one-pot three component reaction (A3-coupling) of the new 1-ethynyl-4-hydroxyanthraquinone with secondary amines and formaldehyde was the main approach for the synthesis of nitrogen substituted 1-[3-(amino)prop-1-ynyl]-4-hydroxyanthraquinones. The influence of different substituent in the amine on reaction rate and yield has been evaluated. The cytotoxicity of 1-ethynyl-4-hydroxyanthraquinones was evaluated using the conventional MTT assay. Among all the compounds synthesized, anthraquinone-propargylamine derivatives 28, 29, 30 and 34 possess most promising cytotoxic potential towards glioblastoma cancer cells; compounds 14 and 19 shown selectivity towards the prostate cancer cells DU-145, and 18, and 24 – towards breast cancer cells MCF-7. The grown inhibition on these cancer cells of 18 and 24 was comparable to those of standard drug Doxorubicin. Molecular modeling of new compounds in DNA G-quadruplex binding site was performed to help understand the observed SAR trends.

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Cytotoxic Stilbenes and Canthinone Alkaloids from Brucea antidysenterica (Simaroubaceae)

Molecules ◽

10.3390/molecules24234412 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4412 ◽

Cited By ~ 2

Author(s):

Yves Salomon Makong ◽

Gervais Mouthé Happi ◽

Judith Liliane Djouaka Bavoua ◽

Jean Duplex Wansi ◽

Lutfun Nahar ◽

...

Keyword(s):

Secondary Metabolites ◽

Ethyl Acetate ◽

Propionic Acid ◽

2D Nmr ◽

Spectroscopic Methods ◽

Phytochemical Study ◽

Methanolic Extracts ◽

New Compounds ◽

Soluble Fractions ◽

Mcf 7

A phytochemical study of the root and bark of Brucea antidysenterica J. F. Mill. (Simaroubaceae) afforded three new compounds, including a stilbene glycoside bruceanoside A (1), and two canthinone alkaloids bruceacanthinones A (3) and B (4), along with ten known secondary metabolites, rhaponticin (2), 1,11-dimethoxycanthin-6-one (5), canthin-6-one (6), 1-methoxycanthin-6-one (7), 2-methoxycanthin-6-one (8), 2-hydroxy-1,11-dimethoxycanthin-6-one (9), β-carboline-1-propionic acid (10), cleomiscosin C (11), cleomiscosin A (12), and hydnocarpin (13). The structures of all the compounds were determined using spectrometric and spectroscopic methods including 1D and 2D NMR, and HRSEIMS. The identities of the known compounds were further confirmed by comparison of their data with those reported in the literature. The root and bark methanolic extracts, the dichloromethane and ethyl acetate soluble fractions, and the isolated compounds (3–13), were assessed for their cytotoxicity against the cancer cell lines A-549, MCF-7, and PC-3. The results suggested that compounds in the extracts might possess a synergic action in their cytotoxicity.

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New approach for the synthesis, docking of new porphyrins and their antitumor activity

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424619500093 ◽

2019 ◽

Vol 23 (03) ◽

pp. 251-259 ◽

Cited By ~ 1

Author(s):

Eman H. Tawfik ◽

Ahmed A. Fadda ◽

Nanees N. Soliman ◽

Laila Abou-Zeid ◽

Amr Negm

Keyword(s):

Molecular Docking ◽

Antitumor Activity ◽

Human Cell ◽

Hepg2 Cells ◽

Human Cell Lines ◽

New Approach ◽

Cytotoxicity Activity ◽

Porphyrin Derivatives ◽

New Compounds ◽

Mcf 7

A new methodology for the synthesis of a new series of mesotetrakis[aryl]-21H,23H-porphyrin derivatives 5a–5d, 6a–6c, 7 and 8 is presented. Structures of new compounds were established based on both elemental and spectral data. Cytotoxicity activity of the newly synthesized compounds was investigated against two human cell lines MCF-7 and HepG2. Molecular docking was performed to investigate the binding between the most active porphyrin derivatives and Bcl-2 molecular biomarkers in HepG2 cells.

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MOLECULAR DOCKING STUDY ON 1H-(3,4d) PYRAZOLO-PYRIMIDINES AS CYCLIN DEPENDANT KINASE (CDK2) INHIBITORS

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2017v9i1.16625 ◽

2016 ◽

Vol 9 (1) ◽

pp. 94

Author(s):

Manisha S. Phoujdar ◽

Gourishankar R. Aland

Keyword(s):

Data Bank ◽

Docking Study ◽

Docking Studies ◽

Van Der Waals Interactions ◽

Binding Modes ◽

Molecular Docking Study ◽

Discovery Studio ◽

Receptor Assays

Objective: CDK2 inhibitors are implicated in several carcinomas viz. Carcinoma of lung, bladder, sarcomas and retinoblastoma. Pyrazolopyrimidines, being purine bioisosters inhibit more than one type of kinase. In this study, we are studying some novel derivatives of 1H-pyrazolo [3,4d] pyrimidines not reported earlier. The objective of the present study is an attempt towards design and development of 1H-[3,4-] pyrazolo-pyrimidines as CDK2 inhibitors through rational drug design.Methods: The present study has been done on CDK2 structure, PDB ID, 3WBL, co-crystallized with ligand PDY from RCSB protein data bank. A series of seventeen 1H-Pyrazolo [3,4-d] pyrimidines feasible for synthesis was docked on the said CDK2 receptor using Auto Dock 4 version, 1.5.6. Outputs were exported to discovery studio 3.5 client for visual inspection of the binding modes and interactions of the compounds with amino acid residues in the active sites.Results: The results of docking studies revealed that the present series of 1H-Pyrazolo[3,4-d] pyrimidines is showing significant binding through hydrogen bonding, hydrophobic, pi and Van der waals interactions, similar to the ligand PDY. Some conserved H-bond interactions comparable to bioisosters and compounds presently under human trials were noted. Ki values predicted in silico also suggest that the series will show promising CDK2 inhibitory activity.Conclusion: The series designed and docked can be further developed by synthesis and in vitro and in vivo activity. The receptor inhibitory activity can also be checked by specific receptor assays.

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Synthesis, In Silico and In Vivo Evaluation of Novel 1, 3, 4-Thiadiazole Analogues as Novel Anticancer Agents

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190710145939 ◽

2020 ◽

Vol 17 (4) ◽

pp. 434-444 ◽

Cited By ~ 1

Author(s):

Swathi Krishna ◽

Byran Gowramma ◽

Manal Mohammed ◽

Rajagopal Kalirajan ◽

Lakshman Kaviarasan ◽

...

Keyword(s):

Vero Cell ◽

Anticancer Activity ◽

Cell Lines ◽

Binding Interaction ◽

Standard Drug ◽

Discovery Studio ◽

Vero Cell Lines ◽

Mcf 7

Background: 1,3,4-thiadiazole is a lead molécule which is versatile for a wide variety of biological activities and in continuation of our interest in establishing some novel heterocyclic compounds for antitumor activity. Objective: The objective of the study was to synthesize series of 5-(1,3-benzodioxol-5-yl)-1,3,4- thiadiazol-2-amine derivative and evaluated for their possible in vitro and in vivo anticancer activity. Methods: The synthesis of 2-aminonaphthoxy-1,3,4-thiadiazole and 5-(1,3-benzodioxol-5-yl)-1,3,4- thiadiazol-2-amine as intermediates were carried out by cyclization method. A mixture of thiosemicarbazide and naphthoxyacetic acid/piperonylic acid and phosphoryl chloride were subjected to cyclization with phosphorous oxychloride to obtain compound 3. Further compounds 1 and 3 were reacted with different aromatic aldehydes in methanol to form compounds 2a-e and 4a-e. The compounds 2a-e and 4a-e were characterized for the melting points, IR, Proton NMR and Mass spectra. The compounds were further evaluated for their anticancer activity. The docking study was performed using Discovery studio 4.1 (Accelrys) software against DNA-binding domain of STAT3. The compounds were analyzed for the ligand-protein binding interaction(s) by molecular docking into the active site of STAT3β using the CDOCKER protocol of Discovery studio (v4.1). Results: The title compounds were screened for in vitro anticancer on human breastadenocarcinoma cells (MCF-7 and Vero). Compounds 4c, 4d and 2d against MCF 7 and 4d against Vero cell lines were found to be the most active dérivatives with IC50 values of 1.03, 2.81 and 3.45 µg/ml against MCF 7 and 31.81 µg/ml against Vero cell lines, respectively. Conclusion: From the in vivo anticancer studies, it was concluded that the synthesized compounds 4c and 4d displayed anticancer activity comparable to the standard drug, while the rest of the compounds demonstrated mild potency for anticancer studies.

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