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, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said
Keyword(s):  
Molecular Modeling ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

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 Helix-loop-helix proteins LYL1 and E2a form heterodimeric complexes with distinctive DNA-binding properties in hematolymphoid cells.

1996 ◽  
Vol 16 (5) ◽  
pp. 2394-2401 ◽  
Author(s):  
A Miyamoto ◽  
X Cui ◽  
L Naumovski ◽  
M L Cleary
Keyword(s):  
Dna Binding ◽  
Cell Lines ◽  
Target Genes ◽  
Protein Complexes ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Binding Properties ◽  
Helix Loop Helix ◽  
Dna Binding Properties

LYL1 is a basic helix-loop-helix (HLH) protein that was originally discovered because of its translocation into the beta T-cell receptor locus in an acute lymphoblastic leukemia. LYL1 is expressed in many hematolymphoid cells, with the notable exceptions of thymocytes and T cells. Using the yeast two-hybrid system to screen a cDNA library constructed from B cells, we identified the E-box-binding proteins E12 and E47 as potential lymphoid dimerization partners for LYL1. The interaction of LYL1 with E2a proteins was further characterized in vitro and shown to require the HLH motifs of both proteins. Immunoprecipitation analyses showed that in T-ALL and other cell lines, endogenous LYL1 exists in a complex with E2a proteins. A preferred DNA-binding sequence, 5'-AACAGATG(T/g)T-3', for the LYL1-E2a heterodimer was determined by PCR-assisted site selection. Endogenous protein complexes containing both LYL1 and E2a bound this sequence in various LYL1-expressing cell lines and could distinguish between the LYL1 consensus and muE2 sites. These data demonstrate that E2a proteins serve as dimerization partners for the basic HLH protein LYL1 to form complexes with distinctive DNA-binding properties and support the hypothesis that the leukemic properties of the LYL1 and TAL subfamily of HLH proteins could be mediated by recognition of a common set of target genes as heterodimeric complexes with class I HLH proteins.

Xanthone Conjugated Amino Acids as Potential Anticancer and DNA Binding Agents: Molecular Docking, Cytotoxicity and SAR Studies

2019 ◽  
Vol 18 (15) ◽  
pp. 2169-2177 ◽  
Author(s):  
Kadallipura P. Rakesh ◽  
Nanjudappa Darshini ◽  
Honnayakanakalli M. Manukumar ◽  
Hamse K. Vivek ◽  
Mohammed Y.H. Eissa ◽  
...  
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Dna Binding ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Molecular Surface ◽  
Heterocyclic Molecules

Background: Amino acids conjugated with heterocyclic molecules are well known for their effective bioactive properties. In search of effective anticancer agents, a series of xanthone linked amino acids 2-23 were synthesized and tested for in vitro anticancer activity. Methods: In vitro anticancer activity of the synthesized xanthone linked amino acids 2-23 are tested against three different cancer cell lines MCF-7, MDA-MB-435 and A549 by MTT assay and validated by DNA binding and molecular docking approaches. Doxorubicin and ethidium bromide used as standard and positive control respectively. Results: Compounds 7, 8 and 9 exhibited potent anticancer activity against tested cancer cell lines and DNA binding study using methyl green. In the molecular docking study, binding interactions of the most active compounds 7, 8 and 9 were confirmed to molecular surface of DNA. Conclusion: Structure-Activity Relationship (SAR) showed that the aromatic and hydrophobic amino acids (phenylalanine, tyrosine, and tryptophan) favoured the DNA binding studies and anticancer activity whereas, aliphatic amino acids showed least anticancer activity.

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