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

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.

Download Full-text

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

Asian Journal of Chemistry ◽

10.14233/ajchem.2021.23064 ◽

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.

Download Full-text

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

Kongunadu Research Journal ◽

10.26524/krj248 ◽

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.

Download Full-text

Design, Synthesis, Anticancer Evaluation and Molecular Modeling of Novel Estrogen Derivatives

Molecules ◽

10.3390/molecules24030416 ◽

2019 ◽

Vol 24 (3) ◽

pp. 416 ◽

Cited By ~ 8

Author(s):

Abd Amr ◽

Elsayed Elsayed ◽

Mohamed Al-Omar ◽

Hanan Badr Eldin ◽

Eman Nossier ◽

...

Keyword(s):

Breast Cancer ◽

Anticancer Agents ◽

Docking Study ◽

Breast Cancer Cell Lines ◽

Cytotoxic Activities ◽

Molecular Docking Study ◽

Design Synthesis ◽

Elemental Analyses

A series of estrone derivatives 3–8 was designed and synthesized using estrone arylmethylenes 2a,b as starting materials and their structures were confirmed by different spectral data and elemental analyses. All the newly synthesized compounds exhibited potent in vitro and in vivo cytotoxic activities against breast cancer cell lines. In addition, all compounds were subjected to in vitro and in vivo inhibition assays for EGFR and VEGFR-2 kinases as well as p53 ubiquitination activity to obtain more details about their mechanism of action. Based on the promising results, a molecular docking study was investigated for the most representative compound 5a against the two targets, EGFR and VEGFR-2 kinases, to assess its binding affinity, hoping to rationalize and obtain potent anticancer agents in the future.

Download Full-text

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

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22957 ◽

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.

Download Full-text

Azole-hydrazone derivatives: Design, synthesis, in vitro biological evaluation, dual EGFR/HER2 inhibitory activity, cell cycle analysis and molecular docking study as anticancer agents

Bioorganic Chemistry ◽

10.1016/j.bioorg.2017.10.016 ◽

2018 ◽

Vol 76 ◽

pp. 67-80 ◽

Cited By ~ 17

Author(s):

Madlen B. Labib ◽

John N. Philoppes ◽

Phoebe F. Lamie ◽

Esam R. Ahmed

Keyword(s):

Cell Cycle ◽

Molecular Docking ◽

Anticancer Agents ◽

Inhibitory Activity ◽

Docking Study ◽

Biological Evaluation ◽

Cell Cycle Analysis ◽

Molecular Docking Study ◽

Design Synthesis

Download Full-text

Design, Synthesis and in vitro Evaluation of 2-(Quinoline-8-sulfonamido)pentanedioic Acid Analogues as Antiangiogenic and Antitumor Agents on Multiple Myeloma

Asian Journal of Chemistry ◽

10.14233/ajchem.2021.23238 ◽

2021 ◽

Vol 33 (8) ◽

pp. 1764-1770

Author(s):

Avijit Ghosh ◽

Abhijit Saha ◽

Koushik Sarker ◽

Suvasish Mishra ◽

Subrata Sen

Keyword(s):

Multiple Myeloma ◽

Anticancer Agents ◽

Antitumor Agents ◽

In Vitro Study ◽

Binding Mode ◽

Amino Acid Residues ◽

Design Synthesis ◽

Human Multiple Myeloma ◽

Pentanedioic Acid

Thalidomide is presently approved as antiangiogenic and anticancer drug in multiple myeloma. The authors present a number of analogue-based designs of N-(o-carboxybenzoyl)-DL-glutamic acid, a major thalidomide metabolite. The compounds were synthesized and biologically tested in multiple myeloma as anticancer agents. Three compounds inhibited HUVEC proliferation at low micromolar concentrations, indicating that they are antiangiogenic and cytotoxic to human multiple myeloma RPMI8226. The active compounds were tested for antiproliferative activity on HUVECs using the dye exclusion method with trypan blue. Dimethyl-2-(quinoline-8-sulfonamido)pentanedioate (2c), in particular, inhibits VEGFR-2 phosphorylation at the Tyr-1175 residue, as determined by SDS PAGE. The binding mode of (2c) was predicted in silico in order to better understand how it interacts with essential amino acid residues in the VEGFR-2 active site. The binding energy was calculated as -161.41kcal/mol. in vitro Study of the compounds on the Vero cell line shows less toxicity towards the normal endothelial cells than the cancer cells.

Download Full-text

Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

Scientific Reports ◽

10.1038/s41598-021-91473-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fariba Peytam ◽

Ghazaleh Takalloobanafshi ◽

Toktam Saadattalab ◽

Maryam Norouzbahari ◽

Zahra Emamgholipour ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Rat Small Intestine ◽

Molecular Docking Study ◽

Design Synthesis ◽

Mild Conditions ◽

Glucosidase Inhibitors ◽

Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

Download Full-text