scholarly journals Design, Synthesis, Antitumor Activity and Molecular Docking Study of Novel 5-Deazaalloxazine Analogs

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2518
Author(s):  
Sawsan Mahmoud ◽  
Doaa Samaha ◽  
Mosaad S. Mohamed ◽  
Nageh A. Abou Taleb ◽  
Mohamed A. Elsawy ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Tumor Cell ◽  
Cell Lines ◽  
Antitumor Agents ◽  
Binding Free Energy ◽  
Docking Study ◽  
Tumor Cell Lines ◽  
Molecular Docking Study ◽  
Mcf 7

Protein tyrosine kinases (PTKs) are the most potential therapeutic targets for cancer. Herein, we present a sound rationale for synthesis of a series of novel 2-(methylthio), 2-(substituted alkylamino), 2-(heterocyclic substituted), 2-amino, 2,4-dioxo and 2-deoxo-5-deazaalloxazine derivatives by applying structure-based drug design (SBDD) using AutoDock 4.2. Their antitumor activities against human CCRF-HSB-2, KB, MCF-7 and HeLa have been investigated in vitro. Many 5-deazaalloxazine analogs revealed high selective activities against MCF-7 tumor cell lines (IC50: 0.17–2.17 µM) over HeLa tumor cell lines (IC50 > 100 µM). Protein kinase profiling revealed that compound 3h induced multi- targets kinase inhibition including −43% against (FAK), −40% against (CDKI) and −36% against (SCR). Moreover, the Annexin-V/PI apoptotic assay elucidate that compound 3h showed 33% and potentially 140% increase in early and late apoptosis to MCF-7 cells respectively, compared to the control. The structure-activity relationship (SAR) and molecular docking study using PTK as a target enzyme for the synthesized 7-deazaalloaxazine derivatives were investigated as potential antitumor agents. The AutoDock binding affinities of the 5-deazaalloxazine analogs into c-kit PTK (PDB code: 1t46) revealed reasonable correlations between their AutoDock binding free energy and IC50.

scholarly journals Unexpected Synthesis, Single-Crystal X-ray Structure, Anticancer Activity, and Molecular Docking Studies of Certain 2–((Imidazole/Benzimidazol–2–yl)thio)–1–arylethanones

Crystals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 446
Author(s):  
Tarfah Al-Warhi ◽  
Mohamed Said ◽  
Mahmoud El Hassab ◽  
Nada Aljaeed ◽  
Hazem Ghabour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Single Crystal ◽  
Cell Lines ◽  
Docking Study ◽  
Anticancer Activities ◽  
Molecular Docking Study ◽  
X Ray ◽  
Mcf 7

In connection with our research program concerning development of novel effective benzimidazole-based anticancer candidates, herein we describe a new unexpected synthetic route to obtain a series of 2–((imidazole/benzimidazol2–yl)thio)1–arylethanones endowed with promising anti-breast cancer and Cyclin-dependent kinase 2 (CDK2) inhibitory activities. Contrary to expectations, products for the reaction of 2–mercaptoimidazole/benzimidazole 2a,b with β–keto esters 6a–c were unambiguously assigned as 2–((imidazol/benzimidazol2–yl)thio)1–arylethanones 10a–f based on NMR spectroscopy and single-crystal X-ray crystallographic analyses. In vitro anticancer activities for herein reported imidazole/benzimidazoles 10a–f were assessed through a cell-based assay against human breast cancer T4–7D and MCF–7 cell lines. Benzimidazoles 10d–f exerted better anti-proliferative action towards T4–7D and MCF–7 cell lines than their corresponding imidazole counterparts 10a–c. Furthermore, a molecular docking study suggested CDK2 kinase as a potential enzymatic target for benzimidazoles 10d–f, and investigated their possible binding pattern and interactions within CDK2 active site. Thereafter, benzimidazoles 10d–f were in vitro examined for their CDK2 inhibitory action, where they exerted good activity. Finally, several key ADME and druglikeness properties were predicted by the SwissADME online tool. Interestingly, benzimidazoles 10d–f were found to have no violations in all druglikeness rules (Veber, Lipinski, Ghose, Muegge, and Egan). In addition, they had neither PAINS nor structural alerts (Brenks). In conclusion, benzimidazoles 10d–f demonstrated not only a promising anticancer activities but also an acceptable ADME and physicochemical properties especially benzimidazole 10e.

scholarly journals Design, Synthesis, and Molecular Docking Study of Novel Heterocycles Incorporating 1,3,4-Thiadiazole Moiety as Potential Antimicrobial and Anticancer Agents

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1066 ◽  
Author(s):  
Mohamed El-Naggar ◽  
Hanan A. Sallam ◽  
Safaa S. Shaban ◽  
Salwa S. Abdel-Wahab ◽  
Abd El-Galil E. Amr ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Reference Drug ◽  
Human Cancer Cell Lines ◽  
Dhfr Inhibitors

A new series of 5-(3,5-dinitrophenyl)-1,3,4-thiadiazole derivatives were prepared and evaluated for their in vitro antimicrobial, antitumor, and DHFR inhibition activity. Compounds 9, 10, 13, and 16 showed strong and broad-spectrum antimicrobial activity comparable to Amoxicillin and Fluconazole as positive antibiotic and antifungal controls, respectively. Compounds 6, 14, and 15 exhibited antitumor activity against four human cancer cell lines, CCRF-CEM leukemia, HCT-15 colon, PC-3 prostate, and UACC-257 melanoma cell lines using Doxorubicin as a reference drug. Compounds 10, 13, 14, and 15 proved to be the most active DHFR inhibitors with an IC50 range of 0.04 ± 0.82–1.00 ± 0.85 µM, in comparison with Methotrexate (IC50 = 0.14 ± 1.38 µM). The highly potent DHFR inhibitors shared a similar molecular docking mode and made a critical hydrogen bond and arene‒arene interactions via Ser59 and Phe31 amino acid residues, respectively.

Virtual Combinatorial Library Design, Synthesis and In vitro Anticancer Assessment of -2-Amino-3-Cyanopyridine Derivatives

2018 ◽  
Vol 21 (2) ◽  
pp. 138-148 ◽  
Author(s):  
Sanal Dev ◽  
Sunil. R. Dhaneshwar ◽  
Bijo Mathew
Keyword(s):  
Virtual Screening ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Docking Study ◽  
Assay Method ◽  
Molecular Docking Study ◽  
Binding Interaction ◽  
Mcf 7

Aim and Objective: For the development of new class of anticancer agents, a series of novel 2-amino-3-cyanopyridine derivatives were designed from virtual screening with Glide program by setting Topoisomerase II as the target. Materials and Methods: The top ranked ten molecules from the virtual screening were synthesized by microwave assisted technique and investigated for their cytotoxic activity against MCF-7 and A- 549 cell lines by using sulforhodamine B assay method. Results: The most active compound 2-amino-4-(3,5-dibromo-4-hydroxyphenyl)-6-(2,4- dichlorophenyl) nicotinonitrile (CG-5) showed significant cytotoxic profile with (LC50 = 97.1, TGI = 29.9 and GI50 = <0.1 µM) in MCF-7 and (LC50= 93.0, TGI= 50.0 and GI50= <7 µM) in A-549 cell lines. A molecular docking study was performed to explore the binding interaction of CG-5with the active site of Topoisomerase II. Conclusion: It can be concluded that halogen substituent pyridine ring was benefit for cytotoxicity.

A Cellular Study of Inflammatory Responses in Women with Polycystic Ovary Syndrome as: “An In vitro Model of Anti Breast Tumor Response” Anti-Breast Tumor Response

2020 ◽  
Author(s):  
Fatemeh Rezayat ◽  
Mehri Hajiaghaei ◽  
Nazanin Ghasemi ◽  
Mehrnaz Mesdaghi ◽  
Fahimeh Ramezani Tehrani ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Breast Tumor ◽  
Mononuclear Cells ◽  
Polycystic Ovary ◽  
Healthy Controls ◽  
Tumor Cell Lines ◽  
Tnf Α ◽  
Mcf 7

Abstract Background: Although Polycystic Ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age; is unclear whether PCOS increases the risk of subsequent development of, Gynecologic cancers namely breast cancer. The present study we aimed to compare the antitumoral ability of peripheral blood mononuclear cells (PBMCs) of women with PCOS with that of healthy controls using the co-culture system between effector cells and target tumor cell lines. Materials & Methods: PBMCs were isolated from 25 women with PCOS and 25 non hirsute eumenorrheic healthy controls by density gradient centrifugation ficoll. Breast tumor cell lines (MDA-468, MCF-7) were incubated as the two target cells and were cultured adjacent to PBMCs in the transwell co-culture system. Proliferation rate of the effectors cells evaluated by BrdU cell proliferation assay after 48 and 72 hours and T CD3+ lymphocytes were assessed using flow cytometry. TNF-α cytokine production was evaluated in cell culture supernatant by sandwich ELISA technique. Results: After 48 hours incubation with MDA-468 and MCF-7, the mean proliferation score of PBMCs was significantly higher in women with PCOS compared to that of healthy controls (921.04; P=0.021 vs 287.6; P=0.002, respectively). In PCOS women, after 72 hours of incubation, TNF-α concentration was significantly reduced compared to 48-hour cultures (921.04 ± 271.4 pg/dl vs 545.6 ± 151.1 pg/dl at 48 h and 72 h intervals respectively, P<0.05); it was increased in healthy controls. There was no significant difference in CD3+ CD8+ cells between the PCOS group and healthy controls. Conclusion: The ability of PBMCs to produce of TNF-α in women with PCOS decreased gradually; as a result of which they may lack the ability required to form an in vitro efficient antitumor response to breast tumor cell lines. It is assumed that threshold activation of mononuclear cells is reduced in women with PCOS and a low-grade inflammatory condition may provide a positive background for arising myeloid derived suppressor cells (MDSCs).

scholarly journals Am Synthesis, Docking Study and In vitro Anticancer Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines

2021 ◽  
Author(s):  
Kasim S. Hmood ◽  
Ammar A. Razzak Mahmood Kubba ◽  
Redha I Al-bayati ◽  
Abdulrahman M. Saleh
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Docking Study ◽  
Spectroscopic Techniques ◽  
Cytotoxic Assay ◽  
Molecular Docking Study ◽  
Thiourea Derivatives ◽  
Starting Point ◽  
Mcf 7

A new series of flurbiprofen derivatives containing thiosemicarbazide moiety (3-7)  was  synthesized from flurbiprofen as parent nucleus by  esterification, hydrazide formation, and  heating with different  aryl isothiocyanate substituents, respectively. Flurbiprofen was also treated with thiosemicarbazide in the  presence POCl3 as  a catalyst,   to produce 1,3,4 -thiadiazole -2-amine (8). Treatment of (8) with different aryl isothiocyanates  produced thiourea derivatives (9-12).  Also, the reaction of  (8)  with different benzoyl chloride substituents produced benzamide compounds (13-15). Eventually , treatment of (8)  with  ethyl acetoacetate(EAA) produced [1,3,4]thiadiazolo[3,2-a]pyrimidin-7-one (16) .The new compounds were  characterized by spectroscopic techniques :FTIR,  1HNMR, and CHNS analysis. A molecular docking  study for  the  synthesized compounds (3-16), against the Vascular Endothelial Growth Factor receptor (VEGFR-2) was applied   and  it  indicated  that compounds 4,7,13, and 15,exhibited the optimum binding energy of     -6.77, -6.12,-6.68, and -6.43 kcal/mol, respectively. Target compounds were  also assessed  for their  in vitro anticancer effects  in a cell-line study. All  of the compounds tested  showed  the most plausible anticancer activity, compared to a positive control(Sorafenib), using in vitro  MTT cytotoxic assay ,against human breast tumor (MCF-7), and normal WRL-68 cell line. The in vitro results revealed that compounds 4,5,10,11,13, and 15 exhibited the highest inhibitory activity at their IC50 concentrations, against MCF-7 cell lines, as follows (122.7,113.9,95,7. 109.1,40.32 and 112.29µg/mL, respectively. While their cytotoxic effect against normal WRL-68 cell line at  their IC50 concentrations, as follow 210.2, 181.3 ,151.7,278.7,80.28, and 236 µg/mL, respectively, therefore,  such compounds were considered more selective toward MCF-7 than normal WRL-68,and their selectivity index (SI): 1.71,1.59,1.59 ,2.55 ,1.99 , and 2.10,respectively . Among the synthesized compounds, the compound 15 was chosen to screen its effect in vitro through multi-parameter cytotoxic assay against MCF-7 breast cancer implemented in High Content Screening (ArrayScan XTI, Thermo Scientific),which  could be taken in consideration as a starting point for the  development  of new anticancer drugs

scholarly journals Bioactivities of essential oils from different parts of Spiranthera odoratissima (Rutaceae)

Rodriguésia ◽  
2020 ◽  
Vol 71 ◽  
Author(s):  
Fernando Duarte Cabral ◽  
Cassia Cristina Fernandes ◽  
Arthur Barcelos Ribeiro ◽  
Iara Squarisi Squarisi ◽  
Denise Crispim Tavares ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Normal Cell ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Ic50 Values ◽  
Mcf 7

Abstract This paper aims to investigate, for the first time, in vitro antitubercular, antileishmanial and antiproliferative activities of essential oils (EOs) from S. odoratissima leaves and flowers - grown in midwestern Brazil - against Mycobacterium tuberculosis, promastigote forms of Leishmania amazonensis and human tumor cell lines. Antimycobacterial activity of EOs was evaluated in terms of the minimal inhibitory concentration (MIC). EOs from leaves and flowers showed to be active antimicrobials against M. tuberculosis, since MIC values were 150 µg/mL and 162.5 µg/mL, respectively. Both EOs exhibited significant activity against promastigote forms of L. amazonensis; IC50 values (50% growth inhibition) were 14.36 ± 2.02 (EOs from leaves) and 19.89 ± 2.66 µg/mL (EOs from flowers). Antiproliferative activity in normal (GM07492A, lung fibroblasts) and tumor (MCF-7, HeLa and M059J) cell lines was performed by the XTT assay; results were expressed as IC50 (50% cell growth inhibition) and the selective index was calculated. IC50 values of EOs from leaves and flowers obtained in normal cell lines for were 502.97 ± 40.33 µg/mL and 370.60 ± 2.01 µg/mL, respectively. Antiproliferative activity was observed against human tumor cell lines, whose IC50 values were significantly lower than those obtained in normal cell lines of MCF-7 cells (367.57 ± 4.46 µg/mL-EOs from leaves and 357.70 ± 1.85 µg/mL-EOs from flowers) and M059J cells (492.53 ± 56.67 µg/mL-EOs from leaves and 324.90 ± 6.72 µg/mL-EOs from flowers), thus, indicating selectivity. These in vitro results showed that EOs from S. odoratissima may be an antimycobacterial, antiparasitic and antitumor agent.

scholarly journals Anticancer and molecular docking studies of some new pyrazole-1-carbothioamide nucleosides

2019 ◽  
Vol 9 (6) ◽  
pp. 4642-4648 ◽  
Keyword(s):  
Molecular Docking ◽  
Human Cancer ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Reference Drug ◽  
Human Cancer Cell Lines ◽  
Chemical Structures ◽  
Hct 116 ◽  
Mcf 7

Eight pyrazole-1-carbothioamide nucleosides were synthesized through conensation of 3-(4-aminophenyl)-pyrazole-1-carbothioamide derivative 2 with four aldoses (arabinose, mannose, glucose and galactose) and acetylation of the produced nucleosides 3a-d with acetic anhydride in pyridine at room temperature to give their corresponding acetyl derivatives 4a-d. Their chemical structures were confirmed by spectroscopic and elemental analysis. The antiproliferative activity was screened against various human cancer cell lines (MCF-7, HepG2 and HCT-116) in vitro; compound 4b showed a significant IC50 values (8.5±0.72 for MCF-7, 9.4±0.84 for HepG2 and 11.7±0.89 µg/ml for HCT-116) which were close to the reference drug 5-fluorouracil (5-FU). Molecular docking study was utilized to illustrate the ability of the more active compounds 3b and 4b to inhibit thymidylate synthase and compare the results with an antimetabolite drug used in cancer chemotherapy "Raltitrexed".

scholarly journals Synthesis and Biological Evaluation of Phaeosphaeride A Derivatives as Antitumor Agents

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 3043 ◽  
Author(s):  
Victoria Abzianidze ◽  
Petr Beltyukov ◽  
Sofya Zakharenkova ◽  
Natalia Moiseeva ◽  
Jennifer Mejia ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Tumor Cell Lines ◽  
Hct 116 ◽  
Mcf 7

New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor activity studies were carried out on the HCT-116, PC3, MCF-7, A549, К562, NCI-Н929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All of the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 was potent against six cancer cell lines, HCT-116, PC-3, K562, NCI-H929, Jurkat, and RPMI8226, showing a 47, 13.5, 16, 4, 1.5, and 7-fold increase in anticancer activity comparative to those of etoposide, respectively. Compound 1 possessed selectivity toward the NCI-H929 cell line (IC50 = 1.35 ± 0.69 μM), while product 7 was selective against three cancer cell lines, HCT-116, MCF-7, and NCI-H929, each having IC50 values of 1.65 μM, 1.80 μM and 2.00 μM, respectively.

scholarly journals Synthesis and Antiplasmodial Activity of 1,2,3-Triazole-Naphthoquinone Conjugates

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3917 ◽  
Author(s):  
Oramas-Royo ◽  
López-Rojas ◽  
Amesty ◽  
Gutiérrez ◽  
Flores ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Tumor Cell ◽  
Cell Lines ◽  
Antiproliferative Activity ◽  
Antimalarial Activity ◽  
Tumor Cell Lines ◽  
Dihydroorotate Dehydrogenase ◽  
Structure Activity ◽  
Mcf 7

A series of 34 1,2,3-triazole-naphthoquinone conjugates were synthesized via copper-catalyzed cycloaddition (CuAAC). They were evaluated for their in vitro antimalarial activity against chloroquine-sensitive strains of Plasmodium falciparum and against three different tumor cell lines (SKBr-3, MCF-7, HEL). The most active antimalarial compounds showed a low antiproliferative activity. Simplified analogues were also obtained and some structure–activity relationships were outlined. The best activity was obtained by compounds 3s and 3j, having IC50 of 0.8 and 1.2 μM, respectively. Molecular dockings were also carried on Plasmodium falciparum enzyme dihydroorotate dehydrogenase (PfDHODH) in order to rationalize the results.

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