A Computational Study of Anticancer Activity of Curcumin Derivatives Using in silico Drug Designing and Molecular Docking Tools

Background: Postprandial hyperglycemia can be reduced by inhibiting major carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase which is an effective approach in both preventing and treating diabetes. Objective: The aim of this study was to synthesize a series of 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl] benzoic acid derivatives and evaluate α-glucosidase and α-amylase inhibitory activity along with molecular docking and in silico ADMET property analysis. Method: Chlorosulfonation of 2,4-dichloro benzoic acid followed by reaction with corresponding anilines/amines yielded 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic acid derivatives. For evaluating their antidiabetic potential α-glucosidase and α-amylase inhibitory assays were carried out. In silico molecular docking studies of these compounds were performed with respect to these enzymes and a computational study was also carried out to predict the drug-likeness and ADMET properties of the title compounds. Results: Compound 3c (2,4-dichloro-5-[(2-nitrophenyl)sulfamoyl]benzoic acid) was found to be highly active having 3 fold inhibitory potential against α-amylase and 5 times inhibitory activity against α-glucosidase in comparison to standard drug acarbose. Conclusion: Most of the synthesized compounds were highly potent or equipotent to standard drug acarbose for inhibitory potential against α-glucosidase and α-amylase enzyme and hence this may indicate their antidiabetic activity. The docking study revealed that these compounds interact with active site of enzyme through hydrogen bonding and different pi interactions.

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A New Series of Antileukemic Agents: Design, Synthesis, In Vitro and In Silico Evaluation of Thiazole-Based ABL1 Kinase Inhibitors

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200824100408 ◽

2020 ◽

Vol 20 ◽

Author(s):

Ebru Zeytün ◽

Mehlika D. Altıntop ◽

Belgin Sever ◽

Ahmet Özdemir ◽

Doha E. Ellakwa ◽

...

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Cell Line ◽

Antiproliferative Activity ◽

In Silico ◽

K562 Cell ◽

Kinase Inhibitors ◽

K562 Cell Line ◽

Cytotoxic Effects ◽

Atp Binding Site

Background: After the milestone approval of imatinib, more than 25 antitumor agents targeting kinases have been approved, and several promising candidates are in various stages of clinical evaluation. Objectives : Due to the importance of thiazole scaffold in targeted anticancer drug discovery, the goal of this work is the design of new thiazolyl hydrazones as potent ABL1 kinase inhibitors for the management of chronic myeloid leukemia (CML). Methods: New thiazolyl hydrazones (2a-p) were synthesized and investigated for their cytotoxic effects on K562 CML cell line. Compounds 2h, 2j and 2l showed potent anticancer activity against K562 cell line. The cytotoxic effects of these compounds on other leukemia (HL-60, MT-2 and Jurkat) and HeLa human cervical carcinoma cell lines were also investigated. Furthermore, their cytotoxic effects on mitogen-activated peripheral blood mononuclear cells (MA-PBMCs) were evaluated to determine their selectivity. Due to its selective and potent anticancer activity, compound 2j was benchmarked for its apoptosis-inducing potential on K562 cell line and inhibitory effects on eight different tyrosine kinases (TKs) including ABL1 kinase. In order to investigate the binding mode of compound 2j into the ATP binding site of ABL1 kinase (PDB: 1IEP), molecular docking study was conducted using MOE 2018.01 program. The QikProp module of Schrödinger’s Molecular modelling package was used to predict the pharmacokinetic properties of compounds 2a-p. Results: 4-(4-(Methylsulfonyl)phenyl)-2-[2-((1,3-benzodioxol-4-yl)methylene)hydrazinyl]thiazole (2j) showed antiproliferative activity against K562 cell line with an IC50 value of 8.87±1.93 µM similar to imatinib (IC50= 6.84±1.11 µM). Compound 2j was found to be more effective than imatinib on HL-60, Jurkat and MT-2 cells. Compound 2j also showed cytotoxic activity against HeLa cell line similar to imatinib. The higher selectivity index value of compound 2j than imatinib indicated that its antiproliferative activity was selective. Compound 2j also induced apoptosis in K562 cell line more than imatinib. Among eight TKs, compound 2j showed the strongest inhibitory activity against ABL1 kinase enzyme (IC50= 5.37±1.17 µM). According to molecular docking studies, compound 2j exhibited high affinity to the ATP binding site of ABL1 kinase forming significant intermolecular interactions. On the basis of in silico studies, this compound did not violate Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 2j stands out as a potential orally bioavailable ABL1 kinase inhibitor for the treatment of CML.

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IN SILICO CHARACTERIZATION, MOLECULAR DOCKING, AND IN VITRO EVALUATION OF TRIAZOLE DERIVATIVES AS POTENTIAL ANTICANCER AGENTS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2021.v14i2.40053 ◽

2021 ◽

pp. 22-28

Author(s):

HARSHITHA T ◽

VINAY KUMAR T ◽

VINEETHA T

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Anticancer Agents ◽

In Silico ◽

Docking Studies ◽

Pharmacokinetic Parameters ◽

Pancreatic Cell ◽

Triazole Derivatives ◽

Wet Lab

Objective: The objective of the study was to perform in silico molecular docking and in vitro anticancer studies of proposed 1,2,4-triazole derivatives for the determination of their anticancer activity. Methods: A series of 10 triazole compounds with different substituents were drawn in ACD Lab ChemSketch software. Molecular and biological properties were identified using Molinspiration software. The compounds that obeyed Lipinski rule of five are subjected for pharmacokinetic parameters prediction and docking analysis. SwissDock ADME software is used for the prediction of absorption, distribution, metabolism, and elimination. Then, the compounds are docked with target enzymes in Chimera software 1.14 version. The molecular docking studies revealed favorable molecular interactions and binding energies. The compounds that showed good docking results were synthesized through wet lab synthesis and further preceded for in vitro anticancer studies. Results: Three compounds are selected for wet lab synthesis due to their good docking results compared to other compounds. The synthesized compounds are subjected to different in vitro anticancer studies and found to be having potential anticancer activity. Conclusion: The pharmacokinetic and docking studies conclude that the triazole compounds have potential as anticancer agents. The in vitro anticancer studies revealed that the triazole derivatives are having high potency of anticancer activity against pancreatic cell lines.

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Synthesis, Characterization, Biological Screening, ADME and Molecular Docking Studies of 2-Phenyl Quinoline-4-Carboxamide Derivatives

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22583 ◽

2020 ◽

Vol 32 (5) ◽

pp. 1151-1157 ◽

Cited By ~ 1

Author(s):

P. Raghurama Shetty ◽

G. Shivaraja ◽

G. Krishnaswamy ◽

K. Pruthviraj ◽

Vivek Chandra Mohan ◽

...

Keyword(s):

Antibacterial Activity ◽

Molecular Docking ◽

Anticancer Activity ◽

In Silico ◽

Active Sites ◽

Docking Studies ◽

Spectrometric Analysis ◽

Molecular Docking Studies ◽

In Vitro Investigation

In this work, some 2-phenyl quinoline-4-carboxamide derivatives (5a-j) were synthesized via base catalyzed Pfitzinger reaction of isatin and acetophenone followed by C-N coupling reaction using POCl3 and assessed them for their in vitro antimicrobial and anticancer activity. The structure of newly synthesized compound were established by FT-IR, 1H & 13C NMR and Mass spectrometric analysis. The synthesized carboxamides were subjected to preliminary in vitro antibacterial activity as well as for antifungal activity. Results of antibacterial activity were compared with standard antibacterial (ciprofloxocin) and antifungal (fluconozole). Among the tested compounds, 5d, 5f and 5h exhibited promising activity with zone of inhibition ranging from 10 to 25 mm. Further, the anticancer activity determined using MTT assay against two cancer cell lines. Compounds 5b, 5d, 5f and 5h showed good anticancer activity among all the other derivatives. In order to correlate the in vitro results, in silico ADME and Molecular docking studies were carried out for (5a-j). ADME properties results showed that all the compounds obey rule of Five rule except 5a, 5e and 5g compound. Molecular docking studies of the synthesized compounds showed good binding affinity through hydrogen bond interactions with key residues on active sites as well as neighboring residues within the active site of chosen target proteins viz. antibacterial, antifungal and anticancer. Comparison of both results of in silico as well as in vitro investigation suggests that the synthesized compounds may act as potential antimicrobial as well as anticancer agents.

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in silico-Based Virtual Screening and Molecular Docking Analysis of Phytochemicals obtained from Methanolic Extract of Cleome viscosa Linn. by GC-MS Method for its Anticancer Activity

Asian Journal of Chemistry ◽

10.14233/ajchem.2021.23384 ◽

2021 ◽

Vol 33 (12) ◽

pp. 2943-2952

Author(s):

K. Usha S. Pai ◽

Yadav D. Bodke ◽

Suman Manandhar ◽

K. Sreedhara Ranganath Pai

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

In Silico ◽

Methanolic Extract ◽

Growth Factor Receptor ◽

Docking Studies ◽

Gas Chromatography Mass Spectrometry ◽

In Silico Docking ◽

Phytochemical Compounds ◽

Cleome Viscosa

Cleome viscosa belonging to the family Capparidaceae, is a weed with ethano-botanical value found in India. In the present investigation, methanolic extract of Cleome viscosa was analyzed by gas chromatography-mass spectrometry (GC-MS) to identify the important phytochemical constituents. The GC-MS analysis of methanol from whole plant of Cleome viscosa detected the presence of 78 phytochemical compounds. Quantitative phytochemical evaluation of the methanolic extract of Cleome viscosa was performed. These identified compounds were analyzed for their anticancer activity through in silico molecular docking studies. Computation based in silico docking studies were done using maestro interface. Three protein, poly (ADP-ribose) polymerase-1 (PARP-1), epidermal growth factor receptor (EGFR), human papilloma virus (HPV) specific to different cancers were selected for screening of these phytochemicals. Phytomolecules with better activity and binding were shortlisted after XP mode of docking. The dock score, glide energy and 2D binding interactions of the top five phytochemicals with three selected proteins have been discussed. The identified hit could be a potent inhibitor these proteins that further requires experimental validation.

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In Vitro, Molecular Docking, and In Silico Binding Mode Analysis of Organic Compounds for Antimicrobial and Anticancer Activity against Jurkat, HCT116, and A549 Cell Lines.

ChemistrySelect ◽

10.1002/slct.202003025 ◽

2020 ◽

Vol 5 (41) ◽

pp. 12807-12818

Author(s):

Sanay Naha ◽

Shivaraja Govindaiah ◽

Swamy Sreenivasa ◽

Jeevan Kallur Prakash ◽

Sivan Velmathi

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Organic Compounds ◽

Cell Lines ◽

A549 Cell ◽

In Silico ◽

Binding Mode ◽

Mode Analysis

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

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200721102726 ◽

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.

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

Current Bioactive Compounds ◽

10.2174/1573407216999200625222014 ◽

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.

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