scholarly journals Synthesis, in Silico Study, and Anti-Cancer Activity of Thiosemicarbazone Derivatives

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1375
Author(s):  
Belay Zeleke Sibuh ◽  
Piyush Kumar Gupta ◽  
Pankaj Taneja ◽  
Sonia Khanna ◽  
Paratpar Sarkar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Anticancer Activities ◽  
Standard Drug ◽  
Drug Candidates ◽  
Anti Cancer ◽  
In Silico Study ◽  
Assay Result ◽  
Tgf Β1

Thiosemicarbazones are known for their biological and pharmacological activities. In this study, we have synthesized and characterized 3-Methoxybenzaldehyde thiosemicarbazone (3-MBTSc) and 4-Nitrobenzaldehyde thiosemicarbazone (4-NBTSc) using IR, 1HNMR and 13C NMR. The compound’s in vitro anticancer activities against different cell lines were evaluated. Molecular docking, Insilco ADMET, and drug-likeness prediction were also done. The test compounds showed a comparative IC50 and growth inhibition with the standard drug Doxorubicin. The IC50 ranges from 2.82 µg/mL to 14.25 µg/mL in 3-MBTSc and 2.80 µg/mL to 7.59 µg/mL in 4-NBTSc treated cells. The MTT assay result revealed, 3-MBTSc inhibits 50.42 and 50.31 percent of cell growth in B16-F0 and EAC cell lines, respectively. The gene expression showed that tumor suppressor genes such as PTEN and BRCA1 are significantly upregulated in 7.42 and 5.33 folds, and oncogenes, PKC, and RAS are downregulated −7.96 and −7.64 folds, respectively in treated cells. The molecular docking performed on the four targeted proteins (PARP, VEGFR-1, TGF-β1, and BRAFV600E) indicated that both 4-NBTSc and 3-MBTSc potentially bind to TGF-β1 with the best binding energy of −42.34 Kcal/mol and −32.13 Kcal/mol, respectively. In addition, the test compound possesses desirable ADMET and drug-likeness properties. Overall, both 3-MBTSc and 4-NBTSc have the potential to be multitargeting drug candidates for further study. Moreover, 3-MBTSc showed better activity than 4-NBTSc.

scholarly journals Design, Synthesis, Molecular Docking, ADME and Biological Evaluation Studies of Some New 1,3,4-oxadiazole Linked Benzimidazoles as Anticancer Agents and Aromatase Inhibitors

2021 ◽  
Author(s):  
ulviye acar çevik ◽  
Ismail Celik ◽  
Ayşen IŞIK ◽  
Yusuf Özkay ◽  
Zafer Asım Kaplancıklı
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Evaluation Studies ◽  
Biological Evaluation ◽  
Binding Modes ◽  
Anticancer Activities ◽  
Mcf 7

Abstract In this study, due to the potential anticancer effects of the benzimidazole ring system, a series of benzimidazole-1,3,4-oxadiazole derivatives were synthesized and characterized by 1H NMR, 13C NMR, and MS spectra analyses. In the in vitro anticancer assay, all the compounds tested anticancer activities using MTT-based assay against five cancer cell lines (MCF-7, A549, HeLa, C6, and HepG2). Among them, compound 5a exhibited the most potent activity with IC50 values of 5,165±0,211 μM and 5,995±0,264 μM against MCF-7 and HepG2 cell lines. Compound 5a was included in the BrdU test to determine the DNA synthesis inhibition effects for both cell types. Furthermore, compound 5c was also found to be more effective than doxorubicin on the HeLa cell line. The selectivity of anticancer activity was evaluated in NIH3T3 (mouse embryo fibroblast cell line) cell line. In vitro, enzymatic inhibition assays of aromatase enzyme were performed for compound 5a acting on the MCF-7 cell line. For compound 5a, in silico molecular docking against aromatase enzyme was performed to determine possible protein-ligand interactions and binding modes.

Novel Pyrazolyl Benzoxazole Conjugates: Design, Synthesis, Molecular Docking Studies and in vitro Anticancer Activities

2019 ◽  
Vol 16 (8) ◽  
pp. 619-626
Author(s):  
Arunkumar Thiriveedhi ◽  
Ratnakaram Venkata Nadh ◽  
Navuluri Srinivasu ◽  
Narayana Murthy Ganta
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Docking Studies ◽  
Anticancer Activities ◽  
Molecular Docking Studies ◽  
Hybrid Molecules ◽  
Mcf 7

Nowadays, hybrid drugs have gained a significant role in the treatment of different health problems. Most of the hybrid molecules with different heterocyclic moieties were proved to be potent anti-tumor agents in cancer chemotherapy. Hence, the present study is aimed at the evaluation of in vitro anticancer activity of novel hybrid molecules (pyrazolyl benzoxazole conjugates) and to investigate their anticancer activity by molecular docking studies. Designed, synthesized and characterized the novel pyrazolyl benzoxazole conjugates. Anticancer activity of these compounds was determined by SRB assay. Then molecular docking studies were carried out against proto-oncogene tyrosine-protein kinase (ATP-Src, PDB: 2BDF), a putative target for cancer. All the synthesized compound derivatives were evaluated against MCF-7, KB, Hop62 and A549 cancer cell lines. Compounds 9b and 9c exhibited excellent anticancer activities with GI50 values of <0.1 µM against MCF-7 and A549 cell lines. Compound 9e exhibited good antitumor activity on MCF-7 and A-549 with GI50 values of 0.12 µM and 0.19 µM respectively. Compound 9g showed better anticancer activity on A-549 cancer cell line with GI50 of 0.34 µM. The two-hybrid molecules 9b and 9c are found to be comparably potent with the standard drug doxorubicin and may act as drug lead compounds in medicinal chemistry aspect. The present docking investigation proved that having benzoxazole of compound 9c at the position of benzofuran of reference compound (N-acetyl pyrazoline derivative) might be valid for contributing to anti-cancer activity.

Computational Exploration of Anti-Cancer Potential of Guaiane Dimers from Xylopia vielana by Targeting B-Raf Kinase Using Chemo-Informatics, Molecular Docking and MD Simulation Studies

2021 ◽  
Vol 21 ◽  
Author(s):  
Syed Shams ul Hassan ◽  
Syed Qamar Abbas ◽  
Mubashir Hassan ◽  
Hui-Zi Jin
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Md Simulations ◽  
Binding Potential ◽  
Anticancer Activities ◽  
Raf Kinase ◽  
Anti Cancer ◽  
In Silico Study ◽  
Computational Exploration ◽  
Future Drug

Background: Natural products from herbs are prolific to display robust anticancer activities. Objectives: In the current study, B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma, was tested against two guaiane-type sesquiterpene dimers, xylopin E-F, obtained from Xylopia vielana. Methods: In this work, a systematic in silico study using ADMET analysis, bioactivity score forecasts, molecular docking, and its simulations were conducted to understand compounds' pharmacological properties. Results: During ADMET predictions of both the compounds, Xylopin E-F has displayed a safer profile in hepatotoxicity, cytochrome inhibition, and only xylopin F displayed as non-cardiotoxic compared to FDA approved drug vemurafenib. Both the compounds were proceeded to molecular docking experiments using Autodock docking software and both the compounds Xylopin E-F have displayed higher binding potential with -11.5Kcal/mol energy compared to control vemurafenib -10.2 Kcal/mol. All the compounds were further evaluated for their MD simulations and their molecular interactions with the B-Raf kinase complex displayed precise interactions with the active gorge of the enzyme by hydrogen bonding. Conclusions: Overall, xylopin F had a better profile relative to xylopin E and vemurafenib, and these findings indicated that this bio-molecule could be used as an anti-melanoma agent and as a possible anticancer drug in the future. Therefore, this is a systematic optimized in silico approach to creating an anticancer pathway for guaiane dimers against the backdrop of its potential for future drug development.

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 and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1749 ◽  
Author(s):  
Lu Jin ◽  
Meng-Ling Wang ◽  
Yao Lv ◽  
Xue-Yi Zeng ◽  
Chao Chen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Hydroxyl Groups ◽  
Drug Candidates ◽  
Design And Synthesis ◽  
Anti Cancer ◽  
Clinical Drugs

Flavonoids are well-characterized polyphenolic compounds with pharmacological and therapeutic activities. However, most flavonoids have not been developed into clinical drugs, due to poor bioavailability. Herein, we report a strategy to increase the drugability of flavonoids by constructing C(sp2)-O bonds and stereo- as well as regioselective alkenylation of hydroxyl groups of flavonoids with ethyl-2,3-butadienoate allenes. Twenty-three modified flavonoid derivatives were designed, synthesized, and evaluated for their anti-cancer activities. The results showed that compounds 4b, 4c, 4e, 5e, and 6b exhibited better in vitro inhibitory activity against several cancer cell lines than their precursors. Preliminary structure–activity relationship studies indicated that, in most of the cancer cell lines evaluated, the substitution on position 7 was essential for increasing cytotoxicity. The results of this study might facilitate the preparation or late-stage modification of complex flavonoids as anti-cancer drug candidates.

scholarly journals In vitro evaluation and molecular docking analysis of potential anticancer compounds from Annona muricata L.

2021 ◽  
Author(s):  
Pichai Nalini ◽  
Kalibulla Syed Ibrahim ◽  
Durairaj Brindha
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Mass Spectrometry Data ◽  
Annona Muricata ◽  
Anticancer Activities ◽  
Anticancer Compounds ◽  
Cytotoxic Effects ◽  
Standard Drug ◽  
Cytotoxicity Studies

Abstract Annona muricata L. is widely distributed in tropical and subtropical regions around the world. Traditionally this plant has been used as a medicine for multiple ailments including cancer. The present study focussed on the anticancer activities of hydroethanolic extracts of leaves of A. muricata L. on Dalton’s Lymphoma Ascites (DLA) cell line in comparison with standard drug doxorubicin. Cytotoxicity studies have indicated that the phytoconstituents of A. muricata have the ability to selectively target cancer cells (IC50 = 185.585 µg/ml), whereas minimal or negligible cytotoxic effects were observed on normal cells. Gas Chromatography - Mass Spectrometry data revealed the presence of 16 phytoconstituents comprising mainly alkaloids and phenolic compounds. Pharmacokinetic profiling and molecular docking studies using the phytoconstituents were performed in order to gain a better understanding of the putative mechanisms of action leading to the development of improved and affordable therapies.

Furanone-functionalized benzothiazole derivatives: synthesis, in vitro cytotoxicity, ADME, and molecular docking studies

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Asif Husain ◽  
Silky Bedi ◽  
Shazia Parveen ◽  
Shah Alam Khan ◽  
Aftab Ahmad ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Docking Studies ◽  
In Vitro Cytotoxicity ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Benzothiazole Derivatives

Abstract In the present study, a novel series of new furanone-based benzothiazole derivatives (4a-j) were synthesized from 4-(benzo[d]thiazol-2-yl)-4-oxobutanoic acid (3) as potential anticancer agents. In vitro cytotoxicity against three human cancer cell lines (A549, MCF7, and DUI45) revealed substantial activity. Di-substituted compound, 4i emerged as a promising anticancer compound which showed IC50 values of 7.2 ± 0.5, 6.6 ± 1.4, and 7.3 ± 0.1 µM against A549, MCF7, and DUI45 cell lines, respectively. Four compounds 4c, 4e, 4f, and 4i evaluated for their acute toxicity were found to be non-toxic on the two vital organs (liver and heart). Further, these compounds were found to be more efficient and less hepatotoxic in comparison to standard drug doxorubicin. Molecular docking studies carried out with VEGFR-2 revealed compounds 4a and 4i as potential VEGFR-2 kinase inhibitors. In silico ADME evaluation was carried out to estimate and predict drug-likeness. Compound 4i demonstrated the best ADME parameters. Based on the results of docking analyses, ADME, and in vitro cytotoxicity, compound 4i is identified as the lead compound for further development of anticancer agents.

Anti-Cancer and Kinases Inhibitor Activities of Synthesized Heterocyclic Substituted Thiophene Fused with Cyclohexane Derivatives

2017 ◽  
Vol 14 (1) ◽  
pp. 768-774 ◽  
Author(s):  
Abd El-Galil E Amr ◽  
Hassan Z Ghanem ◽  
Mohamed A Al-Omar ◽  
Mohamed M Abdalla ◽  
Mohamed G Assy ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Mechanism Of Action ◽  
Sphingosine Kinase ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Kinase Inhibition ◽  
Wide Range ◽  
Anti Cancer

We herein report the anti-cancer and kinases inhibitor activities of some synthesized heterocyclic substituted thiophene fused with cyclohexane derivatives (Fig. 1) were synthesized before. Sixteen of these compounds were conveniently screened for their in vitro cytotoxicity against a wide range of cell lines, and showed potent activities against lung and leukemic cancer cell lines. The in vivo antilung and antileukemic cancers of the most active in vitro compounds was estimated and founded highly potent and compared to the standard drugs Bevacizumab and Etoposide. In search for the mechanism of action of anticancer activities it was found that these compounds exert its action via sphingosine kinase inhibition and inhibition of p53 ubiquitination.

scholarly journals INSILICO DESIGN, SYNTHESIS AND CHARACTERIZATION OF SOME NOVEL BENZOTHIAZOLE DERIVATIVES AS ANTI-CANCER AGENTS

2017 ◽  
Vol 10 (4) ◽  
pp. 150
Author(s):  
Leena K Pappachen ◽  
Subin Mary Zachariah ◽  
Deepthy Chandran
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Docking Studies ◽  
Design Synthesis ◽  
Standard Drug ◽  
Mass Spectral ◽  
Benzothiazole Derivatives ◽  
Anti Cancer ◽  
Mcf 7

Objectives: Cancer is a disease characterized by uncontrollable, irreversible, independent, autonomous, uncoordinated and relatively unlimited and abnormal over growth of tissues. Breast cancer is the second most common type of cancer after lung cancer. The aim of the study is to carry out the docking studies, synthesis and anti-tumour activities  of Benzothiazole derivatives containing oxadiazole groups or amino groups.Methods: The docking studies of benzothiazole derivatives were done with known anti-cancer targets like oestrogen receptor by using argus lab and auto dock programmes with the standard drug tamoxifen. Based upon  the results obtained from the molecular modeling, the derivatives were selected for the synthesis. The synthesized compounds were characterized by melting point, TLC, IR, 1H NMR, 13CNMR, MASS spectral data and screened for their in- vitro anti-cancer activities.Results: The docking scores obtained for benzothiazole derivatives (BT1,BT2,BT3,BT4) and std.tamoxifen  from the preliminary docking program by using  argusLab  were- 9.68,-9.4,-9.59, -11.1988,-9.71 and  by using autodock program were -6.29, -5.25,-7.19,-7.48,-3.86 respectively. All the four derivatives were synthesized, characterized and subjected to in vitro anticancer screening by MTT assay in breast cancer (MCF-7) cell lines. Compounds DBT1, DBT2, DBT3 were the most active compounds against MCF-7 cell lines with IC50 of 70.0, 64.0 and 65.0, respectively.Conclusion: All the four  derivatives show  good docking scores when compared to standard drug and can be concluded that all the synthesized benzothiazole  ligands show good anti-cancer property.Keywords: Benzothiazole, Oxadiazole, Estrogen receptor, Anticancer targets.

Synthesis of novel 1,4-disubstituted 1,2,3-triazolo-bosentan derivatives – evaluation of antimicrobial and anticancer activities and molecular docking

RSC Advances ◽  
2015 ◽  
Vol 5 (127) ◽  
pp. 105266-105278 ◽  
Author(s):  
K. Easwaramoorthi ◽  
A. Jeya Rajendran ◽  
K. Chennakesava Rao ◽  
Y. Arun ◽  
C. Balachandran ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Anticancer Activities ◽  
One Pot ◽  
One Pot Synthesis

One pot synthesis with good yields. Good antimicrobial activity against 4EMV receptor. Prominent anticancer activity against A549 and SKOV-3 cell lines. Significantin vitrocytotoxicity at 7.81 μg mL−1. Docking mode of1hwith 2XP2 receptor.

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