scholarly journals Design, Synthesis, Molecular Docking and in vitro Evaluation of N-(4-Ethoxyphenylsulfonyl)pyrrolidine-2-carboxylic Acid Analogues as Antiangiogenic and Anticancer Agents on Multiple Myeloma

2021 ◽  
Vol 33 (4) ◽  
pp. 727-733
Author(s):  
A. GHOSH ◽  
A. SAHA ◽  
K. SARKER ◽  
S. MISHRA ◽  
S. SEN
Keyword(s):  
Multiple Myeloma ◽  
Molecular Docking ◽  
Carboxylic Acid ◽  
Anticancer Agents ◽  
Umbilical Vein ◽  
Growth Factor Receptor ◽  
In Vitro Study ◽  
Cytotoxic Action ◽  
Molecular Docking Study

In present work, N-(4-ethoxyphenylsulfonyl)pyrrolidine-2-carboxylic acid analogs were designed, synthesized and biologically evaluated as an antiangiogenic and anticancer agent on multiple myeloma. Compounds 3i, 3k and 3m exhibited the cytotoxic action on human multiple myeloma cell line RPMI8226 with IC50 (μM) value 3.72, 3.89 2.28, respectively. These compounds possessed the antiangiogenic property and are selectively cytotoxic to cancer cells, as observed from the in vitro study of human umbilical vein endothelial cell (HUVEC) and African green monkey epithelial cell (VERO), respectively. Antiproliferative assay of the compounds on HUVECs was carried out using the dye exclusion method with trypan blue. Molecular docking study of compound 3m with vascular endothelial growth factor receptor-2 (VEGFR-2) showed possible interaction with a binding energy -62.27 kcal/mol.

scholarly journals Design, Synthesis, Molecular Docking and in vitro Evaluation of N-(4-Methoxyphenylsulfonyl)pyrrolidine-2-carboxylic Acid Analogues as Antiangiogenic and Anticancer Agents on Multiple Myeloma

2020 ◽  
Vol 32 (12) ◽  
pp. 3079-3086
Author(s):  
K. Sarker ◽  
A. Ghosh ◽  
S. Mishra ◽  
A. Saha ◽  
S. Sen
Keyword(s):  
Multiple Myeloma ◽  
Molecular Docking ◽  
Carboxylic Acid ◽  
Mtt Assay ◽  
Anticancer Agents ◽  
Docking Study ◽  
Potential Candidate ◽  
Molecular Docking Study ◽  
Antiangiogenic Activity

A series of N-(4-methoxyphenylsulfonyl)pyrrolidine-2-carboxylic acid analogs were designed as bioisosteres of a major metabolite of thalidomide, i.e., N-(o-carboxybenzoyl)-D,L-glutamic acid. Compounds 2b, 2d, 2f, 2i and 2k exhibited anticancer activity on multiple myeloma (RPMI 8226) by MTS assay and were tested for primary antiangiogenic activity on HUVEC cell line by MTT assay. Compound 2f was excluded from further study as it was found to be cytotoxic to normal epithelial cells. 2b, 2d, 2i and 2k were found to have primary antiangiogenic activity along with low cytotoxicity on normal vero cells in MTT assay indicating selective cytotoxicity towards highly angiogenic multiple myeloma. Antiproliferative assay of compounds 2b, 2d, 2i and 2k on HUVECs was carried out using the dye exclusion method with trypan blue. Molecular docking study of compound 2b calculated the binding energy -89.78 kcal/mol and displayed five hydrogen bonds with critical amino acid residues. The compounds are potential candidate drugs for advanced investigations.

RATIONAL DESIGN, SYNTHESIS AND IN VITRO EVALUATION OF N-(4-ETHOXYPHENYLSULFONYL)-L-GLUTAMIC ACID ANALOGUES AS ANTIANGIOGENIC AND ANTICANCER AGENTS ON MULTIPLE MYELOMA

INDIAN DRUGS ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 26-35
Author(s):  
Abhijit Saha ◽  
Koushik Sarker ◽  
Avijit Ghosh ◽  
Suvasish Mishra ◽  
Subrata Sen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Glutamic Acid ◽  
Anticancer Agents ◽  
Rational Design ◽  
Umbilical Vein ◽  
Cytotoxic Action ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
African Green Monkey Kidney

We report the rational design, synthesis and evaluation of the anticancer and antiangiogenic activity of the N-(4-ethoxyphenylsulfonyl)-L-glutamic acid analogs on multiple myeloma. From the series, compound 2c, 2f, and 2h exhibit cytotoxic action on human multiple myeloma cell line RPMI8226 with IC50 (μM) value 2.72, 2.24, and 1.81, respectively. These compounds possess the antiangiogenic property and are selectively cytotoxic to cancer cells, as observed from the in vitro study of Human Umbilical Vein Endothelial Cell (HUVEC) and African green monkey kidney epithelial cell (VERO), respectively. The compounds also have an antiproliferative effect on HUVECs, which was carried out using the dye exclusion method with trypan blue. Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) Tyr-1175 phosphorylation inhibition assay showed compound 2f, and 2h to be the active inhibitors of roangiogenic responses mediated by VEGFR-2. A molecular docking study of 2f with VEGFR-2 showed possible interaction with a binding energy of -74.19 kcal/mol.

scholarly journals Identification of Ent-Kaurane Diterpenoid Compounds as Potential Inhibitors of the PI3K Pathway in Nonsmall Cell Lung Cancer Through Molecular Docking Simulations

2021 ◽  
Vol 16 (9) ◽  
pp. 1934578X2110332
Author(s):  
Pham T. Hong Minh ◽  
Tran T. Hoai Van ◽  
Tran Q. Toan ◽  
Le M. Bui ◽  
Nguyen H. Thuan Anh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Cell Lung Cancer ◽  
Anticancer Agents ◽  
Nonsmall Cell Lung Cancer ◽  
Molecular Docking Study ◽  
Vitro Assay ◽  
Reference Drug ◽  
Docking Simulations

Annual mortality of 8.2 million could be attributable to cancer globally, posing a serious health issue; particularly, the high number of nonsmall cell lung cancer (NSCLC) diagnosed cases in recent years highlight the need for development in anticancer agents. In NSCLC, a number of specific inhibitors of phosphatidylinositol-3-kinase (PI3K), Protein kinase B (AKT), and mammalian target of rapamycin are currently under development; however, the early evidence has yielded disappointing results. Ent-kaurane diterpenoid compounds from Cronton tonkinensis have been investigated for several bioactivities such as antibacterial, cytotoxic activity, and so on;; however, lung cancer is not yet studied. In this study, we conducted a molecular docking study of 7 ent-kaurane diterpenoids from C tonkinensis against PI3K targeted anticancer therapies; furthermore, their cytotoxicity effects against A549 lung cancer cells were also evaluated. Obtained results indicated that compounds 7, 6, 2, and 1 exhibited significant inhibitory results in comparison to the reference drug oxaliplatin which suggests further in vitro assay for drug development.

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.

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.

scholarly journals Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study

2021 ◽  
Vol 22 (8) ◽  
pp. 3825
Author(s):  
Beata Tylińska ◽  
Benita Wiatrak ◽  
Żaneta Czyżnikowska ◽  
Aneta Cieśla-Niechwiadowicz ◽  
Elżbieta Gębarowska ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Colon Adenocarcinoma ◽  
Docking Study ◽  
Biological Evaluation ◽  
Dermal Fibroblasts ◽  
Pyrimidine Derivatives ◽  
Molecular Docking Study

In the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitumor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. According to the results, all the tested compounds exhibited inhibitory activity on the proliferation of all lines of cancer cells (colon adenocarcinoma (LoVo), resistant colon adenocarcinoma (LoVo/DX), breast cancer (MCF-7), lung cancer (A549), cervical cancer (HeLa), human leukemic lymphoblasts (CCRF-CEM) and human monocytic (THP-1)). In particular, their feature stronger influence on the activity of P-glycoprotein of cell cultures resistant to doxorubicin than doxorubicin. Tested compounds have more lipophilic character than doxorubicin, which determines their affinity for the molecular target and passive transport through biological membranes. Moreover, the inhibitory potential against topoisomerase II and DNA intercalating properties of synthesized compounds were analyzed via molecular docking.

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.

Discovery of a Highly Potent and Novel Gambogic Acid Derivative as an Anticancer Drug Candidate

2020 ◽  
Vol 20 ◽  
Author(s):  
Huiping Ling ◽  
Hong Li ◽  
Meijun Chen ◽  
Baolong Lai ◽  
Haiming Zhou ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Anticancer Agents ◽  
Docking Study ◽  
Gambogic Acid ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Discovery Studio ◽  
Mcf 7

Background and Purpose: Gambogic acid (GA), a promising anti-cancer agent isolated from the resin of Garcinia species in Southeast Asia, exhibits high potency in inhibiting a wide variety of cancer cells growth. Moreover, the fact that it is amenable to chemical modification makes GA an attractive molecule for the development of anticancer agents. Methods: Gambogic acid-3-(4-pyrimidinyloxy) propyl ester (compound 4) was derived from the reaction between 4-hydroxypropoxy pyrimidine and GA. Its structure was elucidated by comprehensive analysis of ESIMS, HRESIMS, 1 D NMR data. Antitumor activities of compound 4 and GA in vitro against HepG-2, A549 and MCF-7 cells were investigated by MTT assay. FITC/PI dye were used to test apoptosis. The binding affinity difference of compound 4 and GA binding to IKKβ was studied by using Discovery Studio 2016. Results: Compound 4 was successfully synthesized and showed strong inhibitory effects on HepG-2, A549 and MCF-7 cells lines with IC50 value of 1.49 ± 0.11, 1.37 ± 0.06 and 0.64 ± 0.16μM, respectively. Molecular docking study demonstrated that four more hydrogen bonds were established between IKKβ and compound 4, compared with GA. Conclusion: Our results suggested that compound 4 showed significant effects in inducing apoptosis. Further molecular docking study indicated that the introduction of pyrimidine could improve GA’s binding affinity to IKKβ. Compound 4 may serve as a potential lead compound for the development of new anticancer drugs.

scholarly journals Synthesis of novel cytotoxic tetracyclic acridone derivatives and study of their molecular docking, ADMET, QSAR, bioactivity and protein binding properties

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rajkumar Veligeti ◽  
Rajesh Bagepalli Madhu ◽  
Jayashree Anireddy ◽  
Visweswara Rao Pasupuleti ◽  
Vijaya Kumar Reddy Avula ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protein Binding ◽  
Anticancer Agents ◽  
In Vitro Study ◽  
Docking Studies ◽  
Drug Candidates ◽  
Protein Binding Assay ◽  
Potential Ligand ◽  
Acridone Derivatives

AbstractAcridone based synthetic and natural products with inherent anticancer activity advancing the research and generating a large number of structurally diversified compounds. In this sequence we have designed, synthesized a series of tetracyclic acridones with amide framework viz., 3-(alkyloyl/ aryloyl/ heteroaryloyl/ heteroaryl)-2,3-dihydropyrazino[3,2,1-de]acridin-7(1H)-ones and screened for their in vitro anti-cancer activity. The in vitro study revealed that compounds with cyclopropyl-acetyl, benzoyl, p-hydroxybenzoyl, p-(trifluoromethyl)benzoyl, p-fluorobenzoyl, m-fluorobenzoyl, picolinoyl, 6-methylpicolinoyl and 3-nicotinoyl groups are active against HT29, MDAMB231 and HEK293T cancer cell lines. The molecular docking studies performed for them against 4N5Y, HT29 and 2VWD revealed the potential ligand–protein binding interactions among the neutral aminoacid of the enzymes and carbonyl groups of the title compounds with a binding energy ranging from − 8.1394 to − 6.9915 kcal/mol. In addition, the BSA protein binding assay performed for them has confirmed their interaction with target proteins through strong binding to BSA macromolecule. The additional studies like ADMET, QSAR, bioactivity scores, drug properties and toxicity risks ascertained them as newer drug candidates. This study had added a new collection of piperazino fused acridone derivatives to the existing array of other nitrogen heterocyclic fused acridone derivatives as anticancer agents.

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