Synthesis, antibacterial, and cytotoxicity evaluation of oleanolic acid-4-aminoquinoline based hybrid compounds

2021 ◽  
Vol 16 ◽  
Author(s):  
Vuyolwethu Khwaza ◽  
Opeoluwa O. Oyedeji ◽  
Blessing A. Aderibigbe ◽  
Eric Morifi ◽  
Y.T. Fonkui ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Oleanolic Acid ◽  
Cancer Cell ◽  
Antimicrobial Agents ◽  
Klebsiella Oxytoca ◽  
Cancer Cell Lines ◽  
Hybrid Compounds ◽  
Microbial Infections

Aim: To prepare a class of oleanolic-based compounds. Background: Conventional drugs used to treat infectious diseases suffer from limitations such as drug toxicity and drug resistance. The resistance of microbes to antimicrobial agents is a significant challenge in treating microbial infections. Combining two or more drugs with different modes of action to treat microbial infections results in a delay in developing drug resistance by the microbes. However, it is challenging to select the appropriate choice of drugs for combination therapy due to the differences in stability and pharmacokinetic profile of the drugs.Therefore, developing hybrid compounds using the existing drugs is a promising approach to design effective antimicrobial agents. Objectives: To prepare oleanolic-based hybrid compounds followed by characterization, in vitro antibacterial, and cytotoxicity evaluation. Methods:: Oleanolic acid-4-aminoquinoline-based hybrid compounds weresynthesized via esterification and amidation. The compounds werecharacterized using FTIR, NMR, and UHPLC-HRMS. Oleanolic acid was isolated from the flower buds of Syszygium aromaticum (L.) Merr. &.Perry, a specie from Kingdom Plantae, order Mytales in Myrtaceae family. Their antibacterial and cytotoxicity activity was determined against selected strains of bacteria assessed using the microdilution assay and sulforhodamine B assay against selected cancer cell lines. Results: The synthesized hybrid compounds exhibited significant antibacterial activity against the Gram-positive bacteria Enterococcus faecalis (ATCC13047), Bacillus subtilis (ATCC19659), Staphylococcus aureus as well as Gram-negative bacteria,Klebsiella oxytoca (ATCC8724), Escherischia coli (ATCC25922), and Proteus vulgaris (ATCC6380)with minimum inhibitory concentrations of 1.25 mg/mLcompared to oleanolic acid (2.5 mg/mL). Compounds 13 and 14 displayed significant cytotoxic effectsin vitro against the cancer cell lines (MCF-7 and DU 145) compared to the oleanolic acid (IC50 ˃ 200 µM). Conclusion: The present study revealed that the modification of C28 of OA enhanced its biological properties.

scholarly journals Inhibition of Nek2 by Small Molecules Affects Proteasome Activity

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Lingyao Meng ◽  
Kent Carpenter ◽  
Alexis Mollard ◽  
Hariprasad Vankayalapati ◽  
Steven L. Warner ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Cancer Cell Lines ◽  
Proteasome Activity ◽  
Cell Cycle Regulators

Background. Nek2 is a serine/threonine kinase localized to the centrosome. It promotes cell cycle progression from G2 to M by inducing centrosome separation. Recent studies have shown that high Nek2 expression is correlated with drug resistance in multiple myeloma patients.Materials and Methods. To investigate the role of Nek2 in bortezomib resistance, we ectopically overexpressed Nek2 in several cancer cell lines, including multiple myeloma lines. Small-molecule inhibitors of Nek2 were discovered using an in-house library of compounds. We tested the inhibitors on proteasome and cell cycle activity in several cell lines.Results. Proteasome activity was elevated in Nek2-overexpressing cell lines. The Nek2 inhibitors inhibited proteasome activity in these cancer cell lines. Treatment with these inhibitors resulted in inhibition of proteasome-mediated degradation of several cell cycle regulators in HeLa cells, leaving them arrested in G2/M. Combining these Nek2 inhibitors with bortezomib increased the efficacy of bortezomib in decreasing proteasome activityin vitro. Treatment with these novel Nek2 inhibitors successfully mitigated drug resistance in bortezomib-resistant multiple myeloma.Conclusion. Nek2 plays a central role in proteasome-mediated cell cycle regulation and in conferring resistance to bortezomib in cancer cells. Taken together, our results introduce Nek2 as a therapeutic target in bortezomib-resistant multiple myeloma.

Synthesis of hybrids thiazole-quinoline, thiazole-indole and analogs: in vitro anti-proliferative effects on cancer cell lines, DNA binding properties and molecular modeling

2021 ◽  
Author(s):  
Paulo Santos-Júnior ◽  
Igor José dos Santos Nascimento ◽  
Edjan Carlos Dantas da Silva ◽  
Kadja Monteiro ◽  
Johnnatan Freitas ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Dna Binding ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Binding Properties ◽  
Hybrid Compounds ◽  
Convenient Synthesis ◽  
Dna Binding Properties

A convenient synthesis under ultrasound (US) irradiation of 4-thiazolidinone, thiazole, dihydrothiazole, and thiazine hybrid compounds containing quinoline and indole nucleus is described. All the title compounds were characterized by NMR...

scholarly journals Design, Synthesis, and Cell Lines Studies of Oleanolic Acid—Hydrogen Sulfide Donor Hybrids

2021 ◽  
Vol 11 (8) ◽  
pp. 3364
Author(s):  
Fenqin Zhao ◽  
Jinyu Li ◽  
Kexin Yue ◽  
Beibei Song ◽  
Erying Sun ◽  
...  
Keyword(s):  
Cell Lines ◽  
Oleanolic Acid ◽  
Cancer Cell ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Design Synthesis ◽  
Anti Cancer ◽  
First Time ◽  
Donor Moiety

In order to develop new oleanolic acid (OA) derivatives endowed with improved antitumor activities, for the first time, a number of new hybrid compounds were reported by combining OA or 3-oxooleanolic acid with appropriate H2S-donor moiety, coupled via a suitable linker. The anti-tumor evaluation indicated that they exhibited excellent anti-cancer activities against the tested cancer cell lines. Moreover, 18d with 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H2S donor and β-alanine as the linker, showed more potent cytotoxicity against the tested cancer cell lines than OA and 3-oxooleanolic acid, especially for A549 cells. Furthermore, the preferred compound, 18d, preferentially accumulates in cancer cells (13.6 μM) over the matched normal cells LO2 (>100 μM) in vitro. The improved antitumor activity of this hybrid was probably due to its H2S-releasing capability.

ANTITUMOR EFFECT OF SUNITINIB AND BORTEZOMIB ON BREAST CANCER CELL LINE IN VITRO

2017 ◽  
Vol 63 (1) ◽  
pp. 141-145
Author(s):  
Yuliya Khochenkova ◽  
Eliso Solomko ◽  
Oksana Ryabaya ◽  
Yevgeniya Stepanova ◽  
Dmitriy Khochenkov
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Antitumor Effect ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Actual Problem

The discovery for effective combinations of anticancer drugs for treatment for breast cancer is the actual problem in the experimental chemotherapy. In this paper we conducted a study of antitumor effect of the combination of sunitinib and bortezomib against MDA-MB-231 and SKBR-3 breast cancer cell lines in vitro. We found that bortezomib in non-toxic concentrations can potentiate the antitumor activity of sunitinib. MDA-MB-231 cell line has showed great sensitivity to the combination of bortezomib and sunitinib in vitro. Bortezomib and sunitinib caused reduced expression of receptor tyrosine kinases VEGFR1, VEGFR2, PDGFRa, PDGFRß and c-Kit on HER2- and HER2+ breast cancer cell lines

Small Molecular Leads Differentially Active Against HER2 Positive and Triple Negative Breast Cancer Cell Lines

2019 ◽  
Vol 15 (7) ◽  
pp. 738-742 ◽  
Author(s):  
Adnan Badran ◽  
Atia-tul-Wahab ◽  
Sharmeen Fayyaz ◽  
Elias Baydoun ◽  
Muhammad Iqbal Choudhary
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cancer Type

Background:Breast cancer is the most prevalent cancer type in women globally. It is characterized by distinct subtypes depending on different gene expression patterns. Oncogene HER2 is expressed on the surface of cell and is responsible for cell growth regulation. Increase in HER2 receptor protein due to gene amplification, results in aggressive growth, and high metastasis in cancer cells.Methods:The current study evaluates and compares the anti-breast cancer effect of commercially available compounds against HER2 overexpressing BT-474, and triple negative MDA-MB-231 breast cancer cell lines.Results:Preliminary in vitro cell viability assays on these cell lines identified 6 lead molecules active against breast cancer. Convallatoxin (4), a steroidal lactone glycoside, showed the most potent activity with IC50 values of 0.63 ± 0.56, and 0.69 ± 0.59 µM against BT-474 and MDA-MB-231, respectively, whereas 4-[4-(Trifluoromethyl)-phenoxy] phenol (3) a phenol derivative, and Reserpine (5) an indole alkaloid selectively inhibited the growth of BT-474, and MDA-MB-231 breast cancer cells, respectively.Conclusion:These results exhibited the potential of small molecules in the treatment of HER2 amplified and triple negative breast cancers in vitro.

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