Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl) pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies

2020 ◽  
Vol 20 (14) ◽  
pp. 1714-1721
Author(s):  
Hatem A. Abuelizz ◽  
El Hassane Anouar ◽  
Mohamed Marzouk ◽  
Mizaton H. Hasan ◽  
Siti R. Saleh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kojic Acid ◽  
Docking Studies ◽  
Breast Adenocarcinoma ◽  
Amino Acid Residues ◽  
New Class ◽  
Structure Activity ◽  
Tyrosinase Inhibitors ◽  
Mcf 7

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies. Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines. Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets. Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase. Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

scholarly journals Aryl butenoic acid derivatives as a new class of histone deacetylase inhibitors: synthesis, in vitro evaluation, and molecular docking studies

2014 ◽  
Vol 38 ◽  
pp. 338-344 ◽  
Author(s):  
Peruze AYHAN EŞİYOK ◽  
Özlem SEVEN ◽  
Gülüzar EYMUR ◽  
Gamze BORA TATAR ◽  
Didem DAYANGAÇ ERDEN ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Docking Studies ◽  
In Vitro Evaluation ◽  
Molecular Docking Studies ◽  
New Class ◽  
Butenoic Acid

Computational Druglikeness Assessment, Synthesis, Characterization and in vitro Biological Activity Evaluation of some Novel Mixed Metal Complexes of 2-(butan-2-ylidene) hydrazinecarbothioamide

2020 ◽  
Vol 23 ◽  
Author(s):  
Tahmeena Khan ◽  
Iqbal Azad ◽  
Alfred J. Lawrence ◽  
Saman Raza ◽  
Seema Joshi ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Biological Activity ◽  
Molecular Docking ◽  
Metal Complexes ◽  
Docking Studies ◽  
Mixed Metal ◽  
Ic50 Value ◽  
Mixed Metal Complexes ◽  
Mcf 7

Aims and Objectives: The heteronuclear (mixed metal) complexes of Schiff bases have been explored as part of the coordination and bioinorganic chemistry. Five novel mixed metal complexes of (E)-2-(butan-2-ylidene) hydrazinecarbothioamide (2-butanone thiosemicarbazone) were prepared and characterized by different spectroscopic techniques. Molecular docking studies were performed with three proteins for two complexes. The toxicity potential, physicochemical properties and bioactivity scores were also predicted. The complexes were tested against three cell lines and also evaluated for their antibacterial activity. Materials and Methods: The mixed metal complexes were prepared in 1:4 molar ratio of metal salt and ligand. OSIRIS 4.6.1 was used to assess the toxicity whereas Molinspiration 2016.03 was used to calculate the bioactivity scores and other physicochemical properties. Principal Component Analysis (PCA) was performed using the Osiris Property Explorer 4.5.1 for defining and visualizing multidimensional property spaces by assigning dimensions to numerical descriptors. Molecular docking studies were performed with three proteins. The anticancer activity was tested against MCF-7, MDA-MB-231, HepG2 and A549 cell lines using MTT assay whereas antibacterial activity was tested using disc diffusion method. Results and Conclusion: The melting points of the complexes were as high as >3500C, indicating high thermal stability. [CuZn(C5H11N3S)4(SO4)2] exhibited minimum energies against the selected proteins. The bioactivity scores of the complexes were between -0.50 and 0.0. All the prepared complexes showed negative Ames score predicted their non-carcinogenic nature. Against A549 [CuZn(C5H11N3S)4(SO4)2], [CoZn(C5H11N3S)4(SO4)Cl2] and [FeZn(C5H11N3S)4(SO4)2] showed potential in vitro activity. IC50 of these three complexes were 19.69, 37.73 and 38.4 respectively. Against MCF-7, [FeCu(C5H11N3S)4(SO4)2] had IC50 value 53.5. Whereas, against HepG2 [CoZn(C5H11N3S)4(SO4)Cl2] was active having IC50 value 61.8. [CoZn(C5H11N3S)4(SO4)Cl2], [FeCu(C5H11N3S)4(SO4)2] and [FeCo(C5H11N3S)4(SO4)Cl2] were active against S. aureus in the concentration range 2-20 mg/mL. The complexes showed improved biological activity as compared to the monometallic complexes of the same ligand.

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.

Design, Synthesis, In Silico and In Vitro Evaluation of Novel Pyrimidine Derivatives as EGFR Inhibitors

2020 ◽  
Vol 20 ◽  
Author(s):  
Gurubasavaraja S.P. Matada ◽  
Nahid Abbas ◽  
Prasad S. Dhiwar ◽  
Rajdeep Basu ◽  
Giles Devasahayam
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
In Silico ◽  
Docking Studies ◽  
Breast Cancer Cell Lines ◽  
Pyrimidine Derivatives ◽  
Molecular Docking Studies ◽  
Mcf 7

Background: The abnormal signaling from tyrosine kinase causes many types of cancers namely breast cancer, non-small cell lung cancer, and chronic myeloid leukemia. This research reports the in-silico, synthesis, and in-vitro study of novel pyrimidine derivatives as EGFR inhibitors. Objective: The objective of the research study is to discover more promising lead compounds using drug discovery process, in which the rational drug design is achieved by the molecular docking and virtual pharmacokinetic studies. Methods: The molecular docking studies were carried out using discovery studio 3.5-version software. The molecules with good docking and binding energy score were synthesized as well as their structures were confirmed by FT-IR, NMR, Mass and elemental analysis. Subsequently molecules were evaluated for their anticancer activity using MDA-MB-231, MCF-7 and A431 breast cancer cell lines by MTT and tyrosine kinase assay methodology. Results: Pyrimidine derivatives displayed anticancer activity. Particularly, compound R8 shows significant cytotoxicity against MDA-MB-231 with an IC50 18.5 ± 0.6 µM. Molecular docking studies proved that the compound R8 has good binding fitting by forming hydrogen bonds with amino acid residues at ATP binding sites of EGFR. Conclusion: Eight pyrimidine derivatives were designed, synthesized and evaluated against breast cancer cell lines. Compound R8 significantly inhibited the growth of MDA-MB-231 and MCF-7. Molecular docking studies reveled that compound R8 has good fitting by forming different Hydrogen bonding interactions with amino acids at ATP binding site of epidermal growth factor receptor target. Compound R8 was a promising lead molecule that showed better results as compared to other compounds in in-vitro studies.

scholarly journals Synthesis, Antiproliferative Activity and Molecular Docking Studies of 1,3,5-Triaryl Pyrazole Compound as Estrogen α Receptor Inhibitor Targeting MCF-7 Cells Line

Molekul ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 18
Author(s):  
Noval Herfindo ◽  
Riska Prasetiawati ◽  
Daniel Sialagan ◽  
Neni Frimayanti ◽  
Adel Zamri
Keyword(s):  
Molecular Docking ◽  
Antiproliferative Activity ◽  
Docking Simulation ◽  
Docking Studies ◽  
Biological Evaluation ◽  
One Pot ◽  
Vitro Assay ◽  
Oxidative Aromatization ◽  
Mcf 7

This research has been successfully synthesized three compounds of 1,3,5-triaryl pyrazole derivatives by two steps reaction. Firstly, pyrazoline (4a-c) compound was obtained by one-pot reaction of aromatic ketones, aldehyde and hydrazine in basic condition. Then, pyrazole (5a-c) compound was obtained by oxidative aromatization of compound 4 in the presense of acetic acid. Chemical structure of predicted molecules was confirmed by FTIR, NMR and HRMS spectroscopy data analysis. Antiproliferative activity of compound 5a-c were evaluated by in vitro assay against MCF-7 cells line and molecular docking simulation against ERα (PDB ID: 3ERT) using MOE 2019. Biological evaluation result showed that pyrazole compounds had weak antiproliferative activity against MCF-7 cells with IC50 were > 1000 µM, whereas the docking studies agrees the result.

Synthesis and In-silico identification of new bioactive 1,3,4-oxadiazole tagged 2,3-dihydroimidazo[1,2-a]pyridine derivatives

2020 ◽  
Vol 16 ◽  
Author(s):  
Bhagwat S. Jadhav ◽  
Vipul P. Purohit ◽  
Ramesh S. Yamgar ◽  
Rajesh S. Kenny ◽  
Suraj N. Mali ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
In Silico ◽  
Antitubercular Activity ◽  
Docking Studies ◽  
Pyridine Derivatives ◽  
Molecular Docking Studies ◽  
New Class ◽  
In Silico Molecular Docking

Background: Tuberculosis (TB) continues to be the most threatening cause of death in recent years. There is urgent need of search more potent, less toxic antitubercular agents. Methods: A set of five new 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives (4a-4e) was synthesized and screened invitro for their antibacterial activity against Mycobacterium tuberculosis (H37 RV strain) ATCC No-27294. Results: Compound 4b displayed potent antitubercular activity at MIC 6.25 µg/mL. In-silico molecular docking studies were performed for evaluation of the binding patterns of compounds 4a-4e in the binding site of proteins like, Pantothenate synthatase and enoyl acyl reductase inhibitor. The outcomes of the in- vitro antitubercular studies were in well agreement with the molecular docking studies. These newly synthesized compounds were found to have good ADMET profile. We also explored possible anticancer activity using in-silico methods. Conclusion: These results shows that readily synthesized 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives (4a-4e) are attracting new class of potent anti-TB targets as well as possible anticancer activity that worth additional opportunities for improvements.

Guanidinyl and Amide Conjugated Benzothiazoles as Potential Anti- Tubercular Agent and their Cytotoxicity Study

2018 ◽  
Vol 16 (2) ◽  
pp. 121-128
Author(s):  
Mahesh Bhat ◽  
S.L. Belagali
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Positive Control ◽  
Docking Studies ◽  
Benzothiazole Derivatives ◽  
Excellent Activity ◽  
Ic50 Values ◽  
Tuberculosis Activity ◽  
Mcf 7

Background: Two series of Guanidinyl benzothiazole and benzothiazole diamide derivatives were synthesized and screened for their anti-mycobacterial activity and cytotoxicity on cancer cell lines. Methods: The anti-mycobacterium study indicates that all the synthesized benzothiazole compounds were appreciably active and some of the compounds have MIC values lower than the standard drugs. Benzothiazoleguanidinyl derivatives (13a, 13b and 13f) showed the excellent activity with MIC values 1.6 µg/mL. The guanidinyl group and electron donating group present in the molecule interacts with the microorganism and arrest the further growth, indicating excellent activity by these compounds. These benzothiazole derivatives were also tested for cytotoxicity against MCF-7 and KB Mouth cell lines by MTT assay and they were found to be moderately active. Results: For the KB-Mouth cell lines, diamide compounds (9a-9h) have remarkable activity and they showed IC50 values at 10 µg/mL. Compared to benzothiazole diamides, Benzothiazole guanidinyl compounds selectively acted as a good anti-mycobacterium agent. Conclusion: In order to rationalize the in-vitro anti-tuberculosis activity, we carried out molecular docking studies with enoyl acyl carrier reductase (InhA) of M. tuberculosis and they exhibited remarkable docking scores from -5.85 to -9.27, which was comparable with the positive control Isoniazid (INH) with -6.61 as the docking score and showed less affinity towards the DprE1 protiens.

scholarly journals Design, Synthesis and in vitro Cytotoxicity Evaluation of New Fluorinated Ionic Salt (S)-(+)-2,3-Dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione as Strategies for Improving Anticonvulsant Activity

2020 ◽  
Vol 32 (4) ◽  
pp. 975-980 ◽  
Author(s):  
V. Natchimuthu ◽  
S. Ravi ◽  
Murugan Ramalingam ◽  
V. Renuga
Keyword(s):  
In Vitro Cytotoxicity ◽  
Breast Adenocarcinoma ◽  
Adenocarcinoma Cell Line ◽  
Design Synthesis ◽  
Ionic Salt ◽  
Structure Activity ◽  
Preliminary Study ◽  
Clinical Drugs ◽  
Mcf 7

The reaction of (S)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione (1) with 4-(trifluoromethyl)benzoic acid (2, C8H5F3O2) in dimethylformamide leads to the formation of C8H5F3O2 (1) as a classical ionic salt 3. The structure of new compound has been characterized by FTIR, 1H NMR, 13C NMR, HRMS spectroscopy. The new compound was tested for in vitro cytotoxicity evaluation by MTT assay against breast adenocarcinoma cell line of MCF-7 cells. A new compound 3 (IC50:199 μM) emerged as minimal toxic when compared to clinical drugs carbamazepine, topiramate and benzodiazepine. A preliminary study of structure activity relationship revealed that the incorporation of fluoro or trifluoromethyl moiety into the compound, even through ionic bond formation, had a great effect on the biological activity and with less toxicity or side effects.

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