Synthesis of Amino Acid–Naphthoquinones and In Vitro Studies on Cervical and Breast Cell Lines

Rivera-Ávalos, Ernesto; Loera, Denisse de; Araujo-Huitrado, Jorge Gustavo; Escalante-García, Ismailia Leilani; Muñoz-Sánchez, Miguel Antonio; Hernández, Hiram; López, Jesús Adrián; López, Lluvia I.

doi:10.3390/molecules24234285

Cited by 16 publications

(30 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compounds 1, 3 , 33 2 , 34 5 , 9 , 35 and 8 ( 36 ) have been achieved according to the cited references. For compound 10 ( 37 ) we applied a different synthetic route with respect to the literature; thus its experimental properties have been reported herein as follows.…”

Section: Resultsmentioning

confidence: 99%

Multitarget Biological Profiling of New Naphthoquinone and Anthraquinone-Based Derivatives for the Treatment of Alzheimer’s Disease

Campora

Canale

Gatta

et al. 2021

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Two series of naphthoquinone and anthraquinone derivatives decorated with an aromatic/heteroaromatic chain have been synthesized and evaluated as potential promiscuous agents capable of targeting different factors playing a key role in Alzheimer’s disease (AD) pathogenesis. On the basis of the in vitro biological profiling, most of them exhibited a significant ability to inhibit amyloid aggregation, PHF6 tau sequence aggregation, acetylcholinesterase (AChE), and monoamine oxidase (MAO) B. In particular, naphthoquinone 2 resulted as one of the best performing multitarget-directed ligand (MTDL) experiencing a high potency profile in inhibiting β-amyloid (Aβ 40 ) aggregation (IC 50 = 3.2 μM), PHF6 tau fragment (91% at 10 μM), AChE enzyme (IC 50 = 9.2 μM) jointly with a remarkable inhibitory activity against MAO B (IC 50 = 7.7 nM). Molecular modeling studies explained the structure–activity relationship (SAR) around the binding modes of representative compound 2 in complex with hMAO B and hAChE enzymes, revealing inhibitor/protein key contacts and the likely molecular rationale for enzyme selectivity. Compound 2 was also demonstrated to be a strong inhibitor of Aβ 42 aggregation, with potency comparable to quercetin. Accordingly, atomic force microscopy (AFM) revealed that the most promising naphthoquinones 2 and 5 and anthraquinones 11 and 12 were able to impair Aβ 42 fibrillation, deconstructing the morphologies of its fibrillar aggregates. Moreover, the same compounds exerted a moderate neuroprotective effect against Aβ 42 toxicity in primary cultures of cerebellar granule cells. Therefore, our findings demonstrate that these molecules may represent valuable chemotypes toward the development of promising candidates for AD therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

Multitarget Biological Profiling of New Naphthoquinone and Anthraquinone-Based Derivatives for the Treatment of Alzheimer’s Disease

Campora

Canale

Gatta

et al. 2021

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“… 15 MCF7 cells have been used as a model for BC 16 , 17 since 1973, 18 and several compounds have been used to evaluate their potential in cancer treatment. 19 , 20 …”

Section: Introductionmentioning

confidence: 99%

Gold(I)-Catalyzed Synthesis of 4H-Benzo[d][1,3]oxazines and Biological Evaluation of Activity in Breast Cancer Cells

et al. 2022

Self Cite

View full text Add to dashboard Cite

The first gold(I)-catalyzed cycloisomerization procedure applied to the synthesis of substituted 4 H -benzo[ d ][1,3]oxazines has been developed starting from N -(2-alkynyl)aryl benzamides. The chemoselective oxygen cyclization via the 6- exo -dig pathway yielded the observed heterocycles in modest to good chemical yields under very mild reaction conditions. The obtained oxazines were assayed on the breast cancer (BC)-derived cell lines MCF-7 and HCC1954 with differential biological activity. The newly synthesized 4 H -benzo[ d ][1,3]oxazine compounds showed several degrees of cell proliferation inhibition with a remarkable effect for those compounds having a substituted aryl at C-2 of the molecules. The 4 H -benzo[ d ][1,3]oxazines showed an IC 50 ranking from 3.1 to 95 μM in MCF-7 and HCC1954 cells. These compounds represent potential drug candidates for BC treatment. However, additional assays are needed to elucidate their complete effect over the cellular and molecular hallmarks of cancer.

show abstract

“…An important natural compound found in plants is naphthoquinones (NQ), where 1,4-carbonyl position and hydroxyl groups in the naphthalene ring is frequent. NQ are privileged in design and drug discovery due to their structural properties and biological actions such as antibacterial [7,8], antifungal [9,10], anticancer [11][12][13], antimalarial [14], and antiviral [15]. In most cases, the biological action is related to redox and acid properties, which can be modulated by adding different atoms or groups to NQ [16].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antimicrobial Evaluation of Amino Acid Naphthoquinone Derivatives as Potential Antibacterial Agents

López

Rivera-Ávalos²,

Villarreal-Reyes

et al. 2021

Chemotherapy

Self Cite

View full text Add to dashboard Cite

Background: The synthesis and biological evaluation of 1,4-naphthoquinone derivatives are of great interest since these compounds exhibit strong antibacterial, antifungal, antimalarial, and anticancer activities. The electronic properties of naphthoquinones are usually modulated by attaching functional groups containing nitrogen, oxygen and sulfur atoms, which tune their biological potency and selectivity. Methods: A series of 13 amino acid 1,4-naphthoquinone derivatives were synthesized under assisted microwave and ultrasound conditions. The antibacterial activity compounds was tested against American type Culture Collection (ATCC): Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis, as well two multidrug resistant pathogens: Escherichia coli and Staphylococcus aureus from clinical isolated. Minimal inhibitory concentration (MIC) was determined using the broth microdilution method. Results: MIC of derivatives 4–11, 14 and 16 showed antimicrobial activity against gram-positive and gram-negative bacteria. Antimicrobial activities of the compounds 4–8 and 14 were ≤MIC 24.7 μg∙mL-1 against all the reference strain, even more the compound 6 showed the most potent activity with a MIC of 3.9 μg∙mL-1 on S. aureus. On the clinical isolated the compounds 7, 8 and 14 showed a MIC of 49.7 and 24.7 μg∙mL-1 against S. aureus y E. coli respectively. About ADME properties and Osiris analysis, the compounds 4-16 presented high gastrointestinal absorption and good characteristics for oral bioavailability and the compound 14 was the less toxic. Conclusion: amino acid 1,4-naphthoquinone derivatives showed good in vitro antibacterial activity against clinical strains, and modifications on C-3 with cloride atom enhanced the efficiency against same pathogens.

show abstract

Synthesis of Amino Acid–Naphthoquinones and In Vitro Studies on Cervical and Breast Cell Lines

Cited by 16 publications

References 45 publications

Multitarget Biological Profiling of New Naphthoquinone and Anthraquinone-Based Derivatives for the Treatment of Alzheimer’s Disease

Multitarget Biological Profiling of New Naphthoquinone and Anthraquinone-Based Derivatives for the Treatment of Alzheimer’s Disease

Gold(I)-Catalyzed Synthesis of 4H-Benzo[d][1,3]oxazines and Biological Evaluation of Activity in Breast Cancer Cells

Synthesis and Antimicrobial Evaluation of Amino Acid Naphthoquinone Derivatives as Potential Antibacterial Agents

Contact Info

Product

Resources

About