Design, synthesis and structure-activity relationship studies of novel spirochromanone hydrochloride analogs as anticancer agents

2022 ◽  
Author(s):  
Surendar Chitti ◽  
Sravani Pulya ◽  
Adinarayana Nandikolla ◽  
Tarun Kumar Patel ◽  
Karan Kumar Banoth ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Growth Factor Receptor ◽  
Docking Study ◽  
Kinase Domain ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Hek 293 ◽  
B16f10 Cells ◽  
Mcf 7

Aim: Literature reports suggest spirochromanone derivatives exhibit anticancer activity. Methodology: The authors designed and synthesized 18 spirochromanone derivatives (Csp 1–18). The compounds were characterized and evaluated for anticancer activity against human breast cancer (MCF-7) and murine melanoma (B16F10) cell lines. Results: The anticancer activity ranged from 4.34 to 29.31 μm. The most potent compounds, Csp 12 and Csp 18, were less toxic against the human embryonic kidney (HEK-293) cell line and ∼ two/∼four fold selective toward MCF-7 than B16F10 in comparison to the reference, BG-45. Csp 12 caused 28.6% total apoptosis, leading to significant cytotoxicity, and arrested the G2 phase of the cell cycle in B16F10 cells. A molecular docking study of Csp 12 exhibited effective binding at the active site of the epidermal growth factor receptor kinase domain. Conclusion: This study highlights the importance of spirochromanones as anticancer agents.

Molecular Design and Synthesis of New 3,4-Dihydropyrimidin-2(1H)-Ones as Potential Anticancer Agents with VEGFR-2 Inhibiting Activity

2019 ◽  
Vol 19 (3) ◽  
pp. 310-322
Author(s):  
Amany S. Mostafa ◽  
Waleed A. Bayoumi ◽  
Mohamed El-Mesery ◽  
Abdelaziz Elgaml
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Molecular Design ◽  
Growth Factor Receptor ◽  
Docking Study ◽  
Structural Features ◽  
Significant Activity ◽  
Inhibiting Activity ◽  
Molecular Docking Study

Background: Two series of 3,4-dihydropyrimidin-2(1H)-one derivatives were designed based on the main structural features characterizing reported anticancer compounds with potent VEGFR-2 inhibiting activity. Methods: All the target compounds were synthesized and investigated for their in vitro anticancer activity using MTT assay and NCI protocol. The most active compounds were further investigated for the VEGFR-2 inhibiting activity using enzyme inhibition assay. Results: Of these derivatives, compound 8b possessed significant activity against Caco-2 (IC50 of 24.9 µM) and MCF7 (IC50 of 29.4 µM), compound 10 showed excellent potency against HCT-116 (IC50 of 32.6 µM), HEPG2 (IC50 of 16.4 µM) and MCF7 (IC50 of 32.8 µM), while compound 11b exhibited moderate anticancer activity towards MCF7 (IC50 of 41.7µM). Both 8b and 10 exhibited good potency regarding the inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2), with an IC50 of 14.00 and 21.62 nM, respectively. Conclusion: The activity was rationalized based on molecular docking study that supported their VEGFR-2 inhibitory activity; as indicated by their favorable binding with the active site.

scholarly journals DESIGN AND ANTICANCER ACTIVITY PREDICTION OF DIHYROPYRIMIDINONE BASED NOVEL INHIBITORS OF P53-MDM2 INTERACTION

2017 ◽  
Vol 10 (16) ◽  
pp. 110
Author(s):  
Surendra Kumar Nayak ◽  
Gopal Lal Khatik ◽  
Rakesh Narang ◽  
Harish Kumar Chopra
Keyword(s):  
Anticancer Activity ◽  
Binding Affinity ◽  
Anticancer Agents ◽  
P53 Protein ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Activity Prediction ◽  
Cycle Regulation ◽  
Mdm2 Inhibitor ◽  
Better Than

  Objective: P53 protein is well known for its role in cell cycle regulation and induction of apoptosis. This protein is degraded by MDM2 mediated proteolysis. Inhibition of interaction between p53 and MDM2 has been recognized as a most potential and selective target for development of novel anticancer agents. Recently, several molecules entered in the clinical trial study for the treatment of various types of cancers are based on inhibition of interaction between p53-MDM2. Therefore, in this study, a novel dihydropyridine based molecules were designed as p53-MDM2 inhibitor, and their anticancer activity (including reference) was determined in comparison with most active anticancer agent and inactive anticancer agents in National Cancer Institute database using “Cancer IN” server.Methods: In this work, a novel dihydropyrimidinone based lead (L11) on the basis of molecular docking study, predicted IC50, anticancer activity, and toxicity profile were designed. Lead L11 was obtained after sequential isosteric replacement of functional groups for optimization in compound L0.Results: The docking scores of L3-L11 found to be in range of 21-25 close to docking score 25 of SAR405838 and better than nutlin-3a. MDM2 binding affinity values (37-78 Kcal/mol) of all ligands were also found to better than that of nutlin-3a (37 Kcal/mol). Surprisingly, MDM2 binding affinity of L11 (78 Kcal/mol) found to be equal to that of SAR405838 and 2-fold greater than nutlin-3a.Conclusion: These data indicating that L11 as a potential lead from dihydropyrimidinones for inhibition of p53-MDM2 interaction.

scholarly journals In Vitro and In Silico Evaluation of Anticancer Activity of New Indole-Based 1,3,4-Oxadiazoles as EGFR and COX-2 Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5190
Author(s):  
Belgin Sever ◽  
Mehlika Dilek Altıntop ◽  
Ahmet Özdemir ◽  
Gülşen Akalın Çiftçi ◽  
Doha E. Ellakwa ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Growth Factor Receptor ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Egfr Inhibition ◽  
Cancer Management ◽  
Cox 2 ◽  
Cox 2 Inhibitors

Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) are crucial targetable enzymes in cancer management. Therefore, herein, new 2-[(5-((1H-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(thiazol/benzothiazol-2-yl)acetamides (2a–i) were designed and synthesized as EGFR and COX-2 inhibitors. The cytotoxic effects of compounds 2a–i on HCT116 human colorectal carcinoma, A549 human lung adenocarcinoma, and A375 human melanoma cell lines were determined using MTT assay. 2-[(5-((1H-Indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(6-ethoxybenzothiazol-2-yl)acetamide (2e) exhibited the most significant anticancer activity against HCT116, A549, and A375 cell lines with IC50 values of 6.43 ± 0.72 μM, 9.62 ± 1.14 μM, and 8.07 ± 1.36 μM, respectively, when compared with erlotinib (IC50 = 17.86 ± 3.22 μM, 19.41 ± 2.38 μM, and 23.81 ± 4.17 μM, respectively). Further mechanistic assays demonstrated that compound 2e enhanced apoptosis (28.35%) in HCT116 cells more significantly than erlotinib (7.42%) and caused notable EGFR inhibition with an IC50 value of 2.80 ± 0.52 μM when compared with erlotinib (IC50 = 0.04 ± 0.01 μM). However, compound 2e did not cause any significant COX-2 inhibition, indicating that this compound showed COX-independent anticancer activity. The molecular docking study of compound 2e emphasized that the benzothiazole ring of this compound occupied the allosteric pocket in the EGFR active site. In conclusion, compound 2e is a promising EGFR inhibitor that warrants further clinical investigations.

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.

scholarly journals Synthesis and molecular docking studies of some novel Schiff bases incorporating 6-butylquinolinedione moiety as potential topoisomerase IIβ inhibitors

2018 ◽  
Vol 5 (6) ◽  
pp. 172407 ◽  
Author(s):  
Hany M. Hassanin ◽  
Rabah A. T. Serya ◽  
Wafaa R. Abd Elmoneam ◽  
Mai A. Mostafa
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Docking Study ◽  
Docking Studies ◽  
Complex Compounds ◽  
Inhibition Activity ◽  
Molecular Docking Study ◽  
Dna Topoisomerase ◽  
Mcf 7

A series of novel pyranoquinolinone-based Schiff's bases were designed and synthesized. They were evaluated for topoisomerase IIβ (TOP2B) inhibitory activity, and cytotoxicity against breast cancer cell line (MCF-7) for the development of novel anticancer agents. A molecular docking study was employed to investigate their binding and functional properties as TOP2B inhibitors, using the D iscovery S tudio 2.5 software, where they showed very interesting ability to intercalate the DNA–topoisomerase complex. Compounds 2a , 2c and 2f showed high docking score values (82.36% −29.98 kcal mol −1 for compound 2a , 78.18% −26.98 kcal mol −1 for compound 2c and 78.65, −28.11 kcal mol −1 for compound 2f ) and revealed the highest enzyme inhibition activity. The best hit compounds exhibited highly potent TOP2B inhibitors with submicromolar IC50 at 5 µM compared to the reference doxorubicin.

scholarly journals INDOLE DERIVATIVES: DESIGN, SYNTHESIS, IN-VITRO BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY AS ANTICANCER AGENTS

2018 ◽  
Vol 5 (1) ◽  
pp. 28-32
Author(s):  
Amuthavalli A ◽  
Prakash B ◽  
Velmurugan R
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Docking Study ◽  
Docking Studies ◽  
Biological Evaluation ◽  
In Vitro Cytotoxicity ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Standard Drug

New hetero annulated indoles were synthesized and structurally characterized by spectral means. In order to understand the nature of interactions of these molecules, we carried out molecular docking studies using the protein kinase CK2 inhibitors. The docking results provided some useful information for the futuredesign of more potent inhibitors. The in vitro cytotoxicity was evaluated for all the new compounds by MTT assay against HeLa and compared with the standard drug ellipticine. All the compounds showed moderate to potent activity against the cell lines. The preliminary structure–activity relationships were carried out.

Design, Synthesis and Biological Potential of 5-(2-Amino-6-(3/4-bromophenyl)pyrimidin-4-yl)benzene-1,3-diol Scaffolds as Promising Antimicrobial and Anticancer Agents

2019 ◽  
Vol 19 (10) ◽  
pp. 851-864 ◽  
Author(s):  
Sanjiv Kumar ◽  
Balasubramanian Narasimhan ◽  
Siong Meng Lim ◽  
Kalavathy Ramasamy ◽  
Vasudevan Mani ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Docking Study ◽  
Binding Pocket ◽  
Dilution Method ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Biological Potential

Background: A series of 5-(2-amino-6-(3/4-bromophenyl)pyrimidin-4-yl)benzene-1,3-diol scaffolds was synthesized by Claisen-Schmidt condensation and characterized by NMR, IR, Mass and elemental analyses. Methods: The synthesized pyrimidine scaffolds were screened for their antimicrobial activity by tube dilution method as well for antiproliferative activity (human colorectal (HCT116) cancer cell line) by SRB assay. Results: The antimicrobial screening results demonstrated that compounds, k6, k12, k14 and k20 were found to be the most potent ones against selected microbial species. The anticancer screening results indicated that compounds, k8 and k14 displayed potent anticancer activity against cancer cell line (HCT116). Conclusion: Further, the molecular docking study carried to find out the interaction between active pyrimidine compounds with CDK-8 protein indicated that compound k14 showed best dock score with better potency within the ATP binding pocket and may be used as a lead for rational drug designing of the anticancer molecule.

Divergent de novo synthesis of 2,4,5-trideoxyhexopyranosides derivatives of podophyllotoxin as anticancer agents

2019 ◽  
Vol 11 (23) ◽  
pp. 3015-3027 ◽  
Author(s):  
Yapeng Lu ◽  
Lu Wang ◽  
Xinyang Wang ◽  
Haoliang Yuan ◽  
Yu Zhao
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
De Novo ◽  
Docking Study ◽  
Inhibitory Effect ◽  
De Novo Synthesis ◽  
Molecular Docking Study ◽  
Cytotoxicity Activity ◽  
Derivatives Of ◽  
Mcf 7

Aim: Identification of new anticancer glycosidic derivatives of podophyllotoxin. Methods: 14 podophyllotoxin D- and L-monosaccharides have been synthesized in three steps employing de novo glycosylation strategy, and their abilities to inhibit the growth of HeLa, HepG2, MCF-7, A549 and MDA-MB-231 cancer cells were investigated by MTT assay. Molecular docking study of compound 5j with tubulin was performed. Immunofluorescence was applied for detecting the inhibitory effect of 5j on tubulin polymerization. Results & conclusion: Most of synthesized compounds showed strong cytotoxicity activity against five cancer cell lines. Compound 5j possessed the highest cytotoxicity with the IC50 values from 41.6 to 95.2 nM, and could concentration-dependently inhibit polymerization of the microtubule cytoskeleton of MCF-7 cells. Molecular docking disclosed that sugar moiety-dedicated hydrogen bond endowed 5j a higher binding affinity for tubulin.

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