scholarly journals Synthesis and Biological Evaluation of Novel Aminochalcones as Potential Anticancer and Antimicrobial Agents

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4129 ◽  
Author(s):  
Joanna Kozłowska ◽  
Bartłomiej Potaniec ◽  
Dagmara Baczyńska ◽  
Barbara Żarowska ◽  
Mirosław Anioł

A series of 18 aminochalcone derivatives were obtained in yields of 21.5–88.6% by applying the classical Claisen-Schmidt reaction. Compounds 4–9, 14 and 16–18 with 4-ethyl, 4-carboxy-, 4-benzyloxy- and 4-benzyloxy-3-methoxy groups were novel, not previously described in the scientific literature. To determine the biological properties of the synthesized compounds, anticancer and antimicrobial activity assays were performed. Antiproliferative potential was evaluated on four different human colon cancer cell lines—HT-29, LS180, LoVo and LoVo/DX —using the SRB assay and compared with green monkey kidney fibroblasts COS7. Anticancer activity was described as the IC50 value. The best results were observed for 2′-aminochalcone (1), 3′-aminochalcone (2) and 4′-aminochalcone (3) (IC50 = 1.43–1.98 µg·mL−1) against the HT-29 cell line and for amino-nitrochalcones 10–12 (IC50 = 2.77–3.42 µg·mL−1) against the LoVo and LoVo/DX cell lines. Moreover, the antimicrobial activity of all derivatives was evaluated on two strains of bacteria: Escherichia coli ATCC10536 and Staphylococcus aureus DSM799, the yeast strain Candida albicans DSM1386 and three strains of fungi: Alternaria alternata CBS1526, Fusarium linii KB-F1 and Aspergillus niger DSM1957. In the case of E. coli ATCC10536 almost all derivatives hindered the bacterial growth (∆OD = 0). Furthermore, the best results were observed in the presence of 4′-aminochalcone (3), that completely limited the growth of all tested strains at the concentration range of 0.25–0.5 mg·mL−1. The strongest bacteriostatic activity was exhibited by novel 3′-amino-4-benzyloxychalcone (14), that prevented the growth of E. coli ATCC10536 with MIC = 0.0625 mg·mL−1.

Author(s):  
Singh Gurvinder ◽  
Singh Prabhsimran ◽  
Dhawan R. K.

In order to develop new antimicrobial agents, a series of 3-formyl indole based Schiff bases were synthesized by reacting 3-formyl indole(indole-3-carboxaldehyde) with substituted aniline taking ethanol as solvent. The reaction was carried in the presence of small amount of p-toluene sulphonic acid as catalyst.All the synthesized compounds were characterized by IR, 1H-NMR spectral analysis. All the synthesized compounds were evaluated for antimicrobial activity against two gram positive bacterial strains (B. subtilisand S. aureus) and two gram negative bacterial strains (P. aeruginosaand E. coli) and one fungal strain (C. albicans). All the synthesized compounds were found to have moderate to good antimicrobial activity. The  standard drug amoxicillin, fluconazole were used for antimicrobial activity. Among the synthesized compounds, the maximum antimicrobial activity was shown by compounds GS04, GS07, GS08 and GS10.


2020 ◽  
Vol 13 (9) ◽  
pp. 229
Author(s):  
Volodymyr Horishny ◽  
Victor Kartsev ◽  
Vasyl Matiychuk ◽  
Athina Geronikaki ◽  
Petrou Anthi ◽  
...  

Herein we report the design, synthesis, computational, and experimental evaluation of the antimicrobial activity of fourteen new 3-amino-5-(indol-3-yl) methylene-4-oxo-2-thioxothiazolidine derivatives. The structures were designed, and their antimicrobial activity and toxicity were predicted in silico. All synthesized compounds exhibited antibacterial activity against eight Gram-positive and Gram-negative bacteria. Their activity exceeded those of ampicillin and (for the majority of compounds) streptomycin. The most sensitive bacterium was S. aureus (American Type Culture Collection ATCC 6538), while L. monocytogenes (NCTC 7973) was the most resistant. The best antibacterial activity was observed for compound 5d (Z)-N-(5-((1H-indol-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)-4-hydroxybenzamide (Minimal inhibitory concentration, MIC at 37.9–113.8 μM, and Minimal bactericidal concentration MBC at 57.8–118.3 μM). Three most active compounds 5d, 5g, and 5k being evaluated against three resistant strains, Methicillin resistant Staphilococcus aureus (MRSA), P. aeruginosa, and E. coli, were more potent against MRSA than ampicillin (MIC at 248–372 μM, MBC at 372–1240 μM). At the same time, streptomycin (MIC at 43–172 μM, MBC at 86–344 μM) did not show bactericidal activity at all. The compound 5d was also more active than ampicillin towards resistant P. aeruginosa strain. Antifungal activity of all compounds exceeded those of the reference antifungal agents bifonazole (MIC at 480–640 μM, and MFC at 640–800 μM) and ketoconazole (MIC 285–475 μM and MFC 380–950 μM). The best activity was exhibited by compound 5g. The most sensitive fungal was T. viride (IAM 5061), while A. fumigatus (human isolate) was the most resistant. Low cytotoxicity against HEK-293 human embryonic kidney cell line and reasonable selectivity indices were shown for the most active compounds 5d, 5g, 5k, 7c using thiazolyl blue tetrazolium bromide MTT assay. The docking studies indicated a probable involvement of E. coli Mur B inhibition in the antibacterial action, while CYP51 inhibition is likely responsible for the antifungal activity of the tested compounds.


2011 ◽  
Vol 76 (12) ◽  
pp. 1597-1606 ◽  
Author(s):  
Nemanja Trisovic ◽  
Bojan Bozic ◽  
Ana Obradovic ◽  
Olgica Stefanovic ◽  
Snezana Markovic ◽  
...  

A series of twelve 3-substituted-5,5-diphenylhydantoins was synthesized, including some whose anticonvulsant activities have already been reported in the literature. Their antiproliferative activities against HCT-116 human colon carcinoma cells were evaluated to determine structure-activity relationships. Almost all of the compounds exhibited statistically significant antiproliferative effects at a concentration of 100 ?M, while the derivative bearing a benzyl group was active even at lower concentrations. Moreover, their in vitro antibacterial activities against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and clinical isolates of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus faecalis and Staphylococcus aureus were evaluated. Only the 3-iso-propyl and 3-benzyl derivatives showed weak antibacterial activities against the Gram-positive bacterium E. faecalis and the Gram-negative bacteria E. coli ATCC 25922 and E. coli.


Author(s):  
Jian-Pei Liu ◽  
Hong-Bo Wei ◽  
Zong-Heng Zheng ◽  
Wei-Ping Guo ◽  
Jia-Feng Fang

AbstractRetinoid resistance has limited the clinical application of retinoids as differentiation-inducing and apoptosis-inducing drugs. This study was designed to investigate whether celecoxib, a selective COX-2 inhibitor, has effects on retinoid sensitivity in human colon cancer cell lines, and to determine the possible mechanism of said effects. Cell viability was measured using the MTT assay. Apoptosis was detected via Annexin-V/PI staining and the flow cytometry assay. PGE2 production was measured with the ELISA assay. The expression of RARβ was assayed via western blotting. The results showed that celecoxib enhanced the inhibitory effect of ATRA in both COX-2 high-expressing HT-29 and COX-2 low-expressing SW480 cell lines. Further study showed the ATRA and celecoxib combination induced greater apoptosis, but that the addition of PGE2 did not affect the enhanced growth-inhibitory and apoptosis-inducing effects of the combination. Moreover, NS398 (another selective COX-2 inhibitor) did not affect the inhibitory effects of ATRA in the two cell lines. Western blotting showed that the expression of RARβ in HT-29 cell lines was increased by celecoxib, but not by NS398, and that the addition of PGE2 did not affect the celecoxib-induced expression of the retinoic acid receptor beta. In conclusion, celecoxib increased the expression of RARβ and the level of cellular ATRA sensitivity through COX-2-independent mechanisms. This finding may provide a potential strategy for combination therapy.


2018 ◽  
Vol 15 (1) ◽  
pp. 21-30
Author(s):  
Deboleena Dhara ◽  
Dhanya Sunil ◽  
Pooja R. Kamath ◽  
K. Ananda ◽  
S. Shrilakshmi ◽  
...  

Introduction: The escalating threat due to dwindling effect of antibiotics and challenge of tackling rising drug-resistant infections has gathered high focus in current medicinal research. Methods: In an attempt to find new molecules that can defeat microbial resistance, two new series of 2-[2-substituted ethenyl]-5-(substituted methoxy)-1,3,4-oxadiazole derivatives were synthesized. Various aromatic hydrazides were allowed to undergo cyclization to substituted oxadiazole-2- amines in the presence of cyanogen bromide and further condensed with different heterocyclic aldehydes to give new oxadiazole derivatives. The synthesized molecules were fully characterized by various spectral techniques and tested for antimicrobial activity. Results: Almost all the newly synthesized compounds especially (5g-5l) displayed remarkable growth inhibition against three bacterial strains: M. smegmatis, S. aureus, E. coli and fungi C. albicans. The antimicrobial activity was further confirmed by MIC assay against the same microorganisms. Oxadiazole 5g displayed promising activity with a MIC value of 0.025 mM for two bacteria and fungi, whereas MIC of this compound for E. coli was 0.1 mM. Other active compounds (5h-5l) also exhibited good MIC ranging between 0.313 to 5.0 mM against the selected microorganisms. Docking simulations were generated to explore the potential binding approaches of ligand 5g at the D-alanine:d-alanine ligase (Ddl) protein of E. coli and S. aureus. Conclusion: Molecule 5g was active even at a lower concentration and could probably act as a prospective lead molecule for targeting the drug resistant microorganisms.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Khaled N. Rashed ◽  
Ana Ćirić ◽  
Jasmina Glamočlija ◽  
Ricardo C. Calhelha ◽  
Isabel C. F. R. Ferreira ◽  
...  

The hydromethanolic extract ofSapindus saponariaL. aerial parts was investigated for antimicrobial activity (against several Gram-positive and Gram-negative bacteria and fungi) and capacity to inhibit the growth of different human tumor cell lines as also nontumor liver cells. The evaluated extract was further characterized in terms of phytochemicals using UV,1H-NMR,13C-NMR, and MS spectroscopic tools. The extract has shown a significant antimicrobial activity on all tested bacterial and fungal species. The best activity was achieved againstBacillus cereusandStaphylococcus aureusamong bacteria and against all threePenicilliumspecies tested. It also revealed cytotoxicity against human colon (HCT-15), cervical (HeLa), breast (MCF-7), and lung (NCI-H460) carcinoma cell lines, with HeLa being the most susceptible tumor cell line. The extract was not toxic for nontumor liver cells. Chromatographic separation of the extract resulted in the isolation and identification of stigmasterol, oleanolic acid, luteolin, luteolin 8-C-β-glucoside (orientin), luteolin 6-C-β-glucoside (isoorientin), luteolin 7-O-β-glucuronide, and rutin. The results of the present findings may be useful for the discovery of novel antitumor and antimicrobial agents from plant origin.


Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3959 ◽  
Author(s):  
Marc ◽  
Araniciu ◽  
Oniga ◽  
Vlase ◽  
Pîrnău ◽  
...  

 In an effort to improve the antimicrobial activity of norfloxacin, a series of hybrid norfloxacin–thiazolidinedione molecules were synthesized and screened for their direct antimicrobial activity and their anti-biofilm properties. The new hybrids were intended to have a new binding mode to DNA gyrase, that will allow for a more potent antibacterial effect, and for activity against current quinolone-resistant bacterial strains. Moreover, the thiazolidinedione moiety aimed to include additional anti-pathogenicity by preventing biofilm formation. The resulting compounds showed promising direct activity against Gram-negative strains, and anti-biofilm activity against Gram-positive strains. Docking studies and ADMET were also used in order to explain the biological properties and revealed some potential advantages over the parent molecule norfloxacin.


2019 ◽  
Vol 38 (4) ◽  
pp. 990-1002 ◽  
Author(s):  
Agnieszka Wróbel ◽  
Beata Kolesińska ◽  
Justyna Frączyk ◽  
Zbigniew J. Kamiński ◽  
Anna Tankiewicz-Kwedlo ◽  
...  

Summary This study provides new information on the cellular effects of 1,3,5-triazine nitrogen mustards with different peptide groups in DLD and Ht-29 human colon cancer cell lines. A novel series of 2,4,6-trisubstituted 1,3,5-triazine derivatives bearing 2-chloroethyl and oligopeptide moieties was designed and synthesized. The most cytotoxic derivative was triazine with an Ala-Ala-OMe substituent on the ring (compound 7b). This compound induced time- and dose-dependent cytotoxicity in the DLD-1 and HT-29 colon cancer cell lines. The triazine derivative furthermore induced apoptosis through intracellular signaling pathway attenuation. Compound 7b may be a candidate for further evaluation as a chemotherapeutic agent against colorectal cancer.


2013 ◽  
Vol 533 (1-2) ◽  
pp. 47-54 ◽  
Author(s):  
Monika Sakowicz-Burkiewicz ◽  
Agnieszka Kitowska ◽  
Marzena Grden ◽  
Izabela Maciejewska ◽  
Andrzej Szutowicz ◽  
...  

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