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1.
Platelets ; 34(1): 2131751, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36331249

RESUMO

Spleen tyrosine kinase (SYK) is an important regulatory molecule of signal transduction pathways involved in the pathogenesis of autoimmune diseases such as immune thrombocytopenia (ITP), and the SYK-signaling pathway has emerged as a potential target for the treatment of numerous diseases. The aim of this narrative review is to summarize the biological properties of SYK and its involvement in disease pathways, provide an update on SYK inhibitors in the treatment of ITP, and consider other potential applications. Fostamatinib, the only licensed SYK inhibitor to date, produces clinical response in ITP patients, including those who are refractory to other treatments. It appears to reduce the risk of thrombotic events and may therefore be a drug to consider for patients with an increased thrombotic risk. Encouraging results have also been obtained in the treatment of warm autoimmune hemolytic anemia. Several other SYK inhibitors have entered clinical trials for a range of indications, reflecting the ability of these drugs to affect multiple signaling pathways. SYK inhibitors have the potential to target several aspects of COVID-19 pathogenesis including thrombosis, without affecting normal hemostasis, and data from the first study of fostamatinib in COVID-19 are encouraging. It is hoped that ongoing trials in autoimmune indications other than ITP, as well as in hematological malignancies and other disorders, confirm the promise of SYK inhibitors.


Immune thrombocytopenia (ITP) is an autoimmune disease that usually happens when your immune system mistakenly attacks and destroys platelets, which are cells that help blood to clot. Individuals with ITP can experience easy or excessive bruising and bleeding. Scientists have identified that an enzyme called spleen tyrosine kinase (SYK) is involved in numerous biological processes that are associated with the immune system response, inflammation, and some types of cancer in humans. Therefore, it has become a target for new drugs which inhibit the action of SYK. In this review article, the authors provide a summary of the biological properties and actions of SYK and its involvement in various diseases, discuss information about drugs that have been developed as SYK inhibitors for the treatment of ITP, and consider other potential uses for drugs that inhibit SYK. Although several drugs are being developed, the only SYK inhibitor that is currently available for the treatment of ITP is a drug called fostamatinib. In patients with ITP, including those who no longer respond to other treatments, fostamatinib has been shown to improve platelet counts and reduce bleeding events. Researchers are also currently investigating the use of drugs that inhibit SYK, including fostamatinib, for the potential treatment of other diseases associated with inflammation (e.g. rheumatoid arthritis, COVID-19), autoimmunity (e.g. warm autoimmune hemolytic anemia), and blood cancers (e.g. lymphoma, chronic lymphocytic leukemia, and acute myeloid leukemia).


Assuntos
COVID-19 , Oxazinas , Púrpura Trombocitopênica Idiopática , Piridinas , Humanos , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Oxazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Piridinas/farmacologia , Quinase Syk
2.
J Enzyme Inhib Med Chem ; 38(1): 176-191, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36317648

RESUMO

Herein, a set of pyridine and pyrimidine derivatives were assessed for their impact on the cell cycle and apoptosis. Human breast cancer (MCF7), hepatocellular carcinoma (HEPG2), larynx cancer (HEP2), lung cancer (H460), colon cancers (HCT116 and Caco2), and hypopharyngeal cancer (FADU), and normal Vero cell lines were used. Compounds 8 and 14 displayed outstanding effects on the investigated cell lines and were further tested for their antioxidant activity in MCF7, H460, FADU, HEP2, HEPG2, HCT116, Caco2, and Vero cells by measuring superoxide dismutase (SOD), malondialdehyde content (MDA), reduced glutathione (GSH), and nitric oxide (NO) content. Besides, Annexin V-FITC apoptosis detection and cell cycle DNA index using the HEPG-2 cell line were established on both compounds as well. Furthermore, compounds 8 and 14 were assessed for their EGFR kinase (Wild and T790M) inhibitory activities, revealing eligible potential. Additionally, molecular docking, ADME, and SAR studies were carried out for the investigated candidates.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Animais , Chlorocebus aethiops , Humanos , Receptores ErbB/metabolismo , Inibidores de Proteínas Quinases/metabolismo , Simulação de Acoplamento Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Células Vero , Células CACO-2 , Neoplasias Pulmonares/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Relação Estrutura-Atividade , Mutação , Pirimidinas/farmacologia , Piridinas/farmacologia , Estrutura Molecular
3.
BMC Cancer ; 22(1): 335, 2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35346114

RESUMO

OBJECTIVE: The purpose of this study was to explore the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab (TACE + AC) for unresectable hepatocellular carcinoma (HCC), and the impact of the timing of the combination on it. METHODS: In this single-arm retrospective study, consecutive data of patients with unresectable HCC treated to our hospital from March 2017 to September 2021 were collected. These patients were treated with TACE and started on camrelizumab and apatinib within one week of TACE. Camrelizumab 200 mg intravenously once every three weeks and apatinib 250 mg orally once daily. Repeat TACE treatment was available on an on-demand basis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The univariate and multivariate Cox regression analyses were used to assess the effect of early and late combination on OS and PFS. RESULTS: A total of 80 patients were enrolled in this study. The median OS was 22.1 months (95% confidence interval [CI]: 13.8-30.5 months) and the median PFS was 15.7 months (95% CI: 14.7-16.6 months). The ORR was 58.8% (95% CI: 47.2-69.6) and DCR reached 81.2% (95% CI: 71.0-89.1). Multivariable Cox proportional hazard regression analyses showed that TACE late combined with apatinib and camrelizumab provided better OS than early combination (HR = 0.175, 95% CI:0.060-0.509, P = 0.001), as did PFS (HR = 0.422, 95% CI:0.184-0.967, P = 0.041). All treatment-related adverse events were tolerable, and no serious adverse events were observed. CONCLUSION: TACE combined with apatinib plus camrelizumab for patients with unresectable HCC has promising antitumor activity and a manageable safety profile. For unresectable HCC with large tumor burden, late combination provides better OS and PFS compared to early combination.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Piridinas , Estudos Retrospectivos
4.
Mar Drugs ; 20(11)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36355014

RESUMO

Thallusin, a highly biologically active, phytohormone-like and bacterial compound-inducing morphogenesis of the green tide-forming macroalga Ulva (Chlorophyta), was determined in bacteria and algae cultures. A sensitive and selective method was developed for quantification based on ultra-high-performance liquid chromatography coupled with electrospray ionization and a high-resolution mass spectrometer. Upon C18 solid phase extraction of the water samples, thallusin was derivatized with iodomethane to inhibit the formation of Fe-thallusin complexes interfering with the chromatographic separation. The concentration of thallusin was quantified during the relevant phases of the bacterial growth of Maribacter spp., ranging from 0.16 ± 0.01 amol cell-1 (at the peak of the exponential growth phase) to 0.86 ± 0.13 amol cell-1 (late stationary phase), indicating its accumulation in the growth medium. Finally, we directly determined the concentration of thallusin in algal culture to validate our approach for monitoring applications. Detection and quantification limits of 2.5 and 7.4 pmol L-1, respectively, were reached, which allow for quantifying ecologically relevant thallusin concentrations. Our approach will enable the surveying of thallusin in culture and in nature and will thus contribute to the chemical monitoring of aquaculture.


Assuntos
Clorófitas , Piridinas , Ulva , Bactérias , Cromatografia Líquida de Alta Pressão/métodos , Plantas , Ulva/microbiologia
5.
Molecules ; 27(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36364013

RESUMO

Monoterpene pyridine alkaloids (MTPAs) are alkaloids derived from iridoid glycosides (IGs). The common molecular structure of MTPAs is the pyridine ring, while some of them have a cyclopenta[c]pyridine skeleton. Some compounds containing this structure are potentially bioactive medicinal agents. In this paper, seven drug candidates (A-G), ninety natural source products (1-90), thirty-seven synthesized compounds (91-127), as well as twenty-six key intermediates (S1-S26) were summarized. We categorized five types of MTPAs and one type of cyclopenta[c]pyridine alkaloids in all. Additionally, their possible genetic pathways were proposed. Then, the chemical transformation, biotransformation, chemical synthesis, as well as the bioactivity of MTPAs and cyclopenta[c]pyridine derivatives were analyzed and summarized. Cyclopenta[c]pyridine derivatives can be concisely and chirally synthesized, and they have shown potentials with antibacterial, insecticidal, antiviral, anti-inflammatory, and neuropharmacological activities.


Assuntos
Alcaloides , Produtos Biológicos , Monoterpenos , Alcaloides/farmacologia , Alcaloides/química , Estrutura Molecular , Piridinas/farmacologia , Piridinas/química , Produtos Biológicos/química
6.
Molecules ; 27(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364083

RESUMO

Pyridocoumarins are a class of synthetic and naturally occurring organic compounds with interesting biological activities. This review focuses on the synthetic strategies for the synthesis of pyridocoumarins and presents the biological properties of those compounds. The synthesis involves the formation of the pyridine ring, at first, from a coumarin derivative, such as aminocoumarins, hydroxycoumarins, or other coumarins. The formation of a pyranone moiety follows from an existing pyridine or piperidine or phenol derivative. For the above syntheses, [4 + 2] cycloaddition reactions, multi-component reactions (MCR), as well as metal-catalyzed reactions, are useful. Pyridocoumarins present anti-cancer, anti-HIV, antimalarial, analgesic, antidiabetic, antibacterial, antifungal, anti-inflammatory, and antioxidant activities.


Assuntos
Cumarínicos , Piridinas , Aminocumarinas , Reação de Cicloadição , Antifúngicos/farmacologia
7.
Molecules ; 27(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364101

RESUMO

Tripterygium wilfordii Hook. f. is a well-known traditional Chinese medicine used to treat autoimmune diseases. Sesquiterpene pyridine alkaloids (SPAs) are a major class of components found in this herb that have piqued the interest of researchers due to their complex and diverse structures as well as significant biological activities. In this study, ten new SPAs, wilfordatine A-J (1-10), were isolated from the roots of T. wilfordii, along with ten known analogues (11-20). Their structures were primarily elucidated by extensive 1D and 2D NMR spectroscopic analysis. To search for more immunosuppressive ingredients related to the clinical efficacy of T. wilfordii, the total alkaloids (TA) and compounds 4, 5, and 9-16 were tested for their inhibitory effects on nuclear factor-kappa B (NF-κB) pathway in Lipopolysaccharide (LPS) induced HEK293/NF-κB-Luc cells. Among them, TA, compounds 5, 11, and 16 showed potent immunosuppressive activity, with IC50 values of 7.25 µg/mL, 8.75 µM, 0.74 µM, and 15.66 µM, respectively, and no influence on the cell viability at a concentration of 100 µg/mL (TA) or 100 µM (5, 11, and 16). Accordingly, TA, 5, 11, and 16, especially 11, were identified as promising candidates for further investigation into their potential use as immunosuppressive agents.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Sesquiterpenos , Humanos , Tripterygium/química , NF-kappa B , Células HEK293 , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Alcaloides/farmacologia , Alcaloides/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Piridinas/farmacologia , Piridinas/química , Imunossupressores/farmacologia
8.
Molecules ; 27(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36364219

RESUMO

A series of N-acyl derivatives of anabasine and cytisine were prepared, to discover novel, natural product-based medicinal agents. All synthesized compounds were tested for antimicrobial, antifungal, antiviral and analgesic activity. The most pronounced antibacterial activity was shown by the compounds with isoxazole fragments, while the adamantane derivatives showed the greatest antiviral effect. It was found that the majority of anabasine derivatives showed significant analgesic activity, reducing the pain response of animals to the irritating effect of acetic acid. The presence of a high level of antimicrobial and antiviral activity in newly synthesized compounds makes it possible to consider them promising for further study of their pharmacological properties.


Assuntos
Adamantano , Animais , Anabasina , Azóis , Piridinas , Analgésicos/farmacologia , Antibacterianos/farmacologia , Antivirais/farmacologia , Relação Estrutura-Atividade , Testes de Sensibilidade Microbiana
9.
Molecules ; 27(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36364252

RESUMO

Natural products are an excellent source of inspiration for the development of new drugs. Among them, betalains have been extensively studied for their antioxidant properties and potential application as natural food dyes. Herein, we describe the seven-step synthesis of new betalamic acid analogs without carboxy groups in the 2- and 6-position with an overall yield of ~70%. The Folin-Ciocalteu assay was used to determine the antioxidant properties of protected intermediate 21. Additionally, the five-step synthesis of betalamic acid analog 35 with three ester moieties was performed. Using NMR techniques, the stability of the obtained compounds towards oxygen was analyzed.


Assuntos
Antioxidantes , Pirrolidinas , Antioxidantes/farmacologia , Antioxidantes/química , Betalaínas/química , Piridinas/química
10.
Molecules ; 27(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364369

RESUMO

The synthesis of the products of the 1,3-propanesultone ring opening during its interaction with amides of pyridinecarboxylic acids has been carried out. The dependence of the yield of the reaction products on the position (ortho-, meta-, para-) of the substituent in the heteroaromatic fragment and temperature condition was revealed. In contrast to the meta- and para-substituted substrates, the reaction involving ortho-derivatives at the boiling point of methanol unexpectedly led to the formation of a salt. On the basis of spectroscopic, X-Ray, and quantum-chemical calculation data, a model of the transition-state, as well as a mechanism for this alkylation reaction of pyridine carboxamides with sultone were proposed in order to explain the higher yields obtained with the nicotinamide and its N-methyl analog compared to ortho or meta parents. Based on the analysis of ESP maps, the positions of the binding sites of reagents with a potential complexing agent in space were determined. The in silico evaluation of possible biological activity showed that the synthetized compounds revealed some promising pharmacological effects and low acute toxicity.


Assuntos
Amidas , Piridinas , Piridinas/química , Amidas/química , Betaína , Alquilação
11.
Molecules ; 27(21)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36364469

RESUMO

Antimicrobial resistance is on the rise, and there aren't enough new treatments to combat it. This might send the modern world back to the pre-antibiotic age. The molecular hybrids of pyrazolo[3,4-b]pyridine and triazole have been designed, synthesized, and analyzed for their drug-like molecule nature and in vitro analyses for their inhibition potentials against S. aureus and K. pneumoniae. The compounds 24 and 27 have been identified as the high potential molecules in this series based on in vitro experiments. Compound 24 has zone of inhibition values of 15 ± 0.82 mm and 14 ± 0.7 mm, whilst compound 27 has zone of inhibition values of 18 ± 0.95 mm and 16 ± 0.82 mm against S. aureus and K. pneumoniae, respectively. MIC and MIB values for compounds 24 and 27 against S. aureus and K. pneumoniae are 0.25 and 0.5, respectively.


Assuntos
Staphylococcus aureus , Triazóis , Triazóis/farmacologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Piridinas/farmacologia , Klebsiella pneumoniae , Relação Estrutura-Atividade
12.
PLoS One ; 17(11): e0277455, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36355804

RESUMO

Recently, pesticides have been suggested to be one of the factors responsible for the large-scale decline in honey bee populations, including colony collapse disorder. The identification of the genes that respond to pesticide exposure based on their expression is essential for understanding the xenobiotic detoxification metabolism in honey bees. For the accurate determination of target gene expression by quantitative real-time PCR, the expression stability of reference genes should be validated in honey bees exposed to various pesticides. Therefore, in this study, to select the optimal reference genes, we analyzed the amplification efficiencies of five candidate reference genes (RPS5, RPS18, GAPDH, ARF1, and RAD1a) and their expression stability values using four programs (geNorm, NormFinder, BestKeeper, and RefFinder) across samples of five body parts (head, thorax, gut, fat body, and carcass) from honey bees exposed to seven pesticides (acetamiprid, imidacloprid, flupyradifurone, fenitrothion, carbaryl, amitraz, and bifenthrin). Among these five candidate genes, a combination of RAD1a and RPS18 was suggested for target gene normalization. Subsequently, expression levels of six genes (AChE1, CYP9Q1, CYP9Q2, CYP9Q3, CAT, and SOD1) were normalized with a combination of RAD1a and RPS18 in the different body parts from honey bees exposed to pesticides. Among the six genes in the five body parts, the expression of SOD1 in the head, fat body, and carcass was significantly induced by six pesticides. In addition, among seven pesticides, flupyradifurone statistically induced expression levels of five genes in the fat body.


Assuntos
Inseticidas , Praguicidas , Abelhas/genética , Animais , Praguicidas/toxicidade , Reação em Cadeia da Polimerase em Tempo Real , Superóxido Dismutase-1 , Piridinas/toxicidade , Inseticidas/toxicidade , Inseticidas/metabolismo
13.
J Am Chem Soc ; 144(45): 20955-20963, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36326518

RESUMO

An efficient asymmetric synthesis of a potent KRAS G12C covalent inhibitor, GDC-6036 (1), is reported. The synthesis features a highly atroposelective Negishi coupling to construct the key C-C bond between two highly functionalized pyridine and quinazoline moieties by employing a Pd/Walphos catalytic system. Statistical modeling by comparing computational descriptors of a range of Walphos chiral bisphosphine ligands to a training set of experimental results was used to inform the selection of the best ligand, W057-2, which afforded the desired Negishi coupling product (Ra)-3 in excellent selectivity. A subsequent telescoped reaction sequence of alkoxylation, global deprotection, and acrylamide formation, followed by a final adipate salt formation, furnished GDC-6036 (1) in 40% overall yield from starting materials pyridine 5 and quinazoline 6.


Assuntos
Antineoplásicos , Proteínas Proto-Oncogênicas p21(ras) , Modelos Lineares , Antineoplásicos/farmacologia , Quinazolinas/química , Piridinas
14.
J Am Chem Soc ; 144(45): 20561-20565, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36343210

RESUMO

Caution needs to be exercised in associating changes in plasmon-enhanced Raman spectra with chemical transformations. This is demonstrated through a detailed analysis of tip-enhanced Raman (TER) scattering from 4-mercaptopyridine (MPY) on gold. The substrate used consists of gold nanoplates atop a gold surface featuring heterogeneous grooves, all coated with a monolayer of MPY. The brightest spectra across the substrate exhibit features that can only be recovered by considering the generalized polarizability of oriented MPY molecules. The complex TER spectra we observe do not mark interfacial chemistry but rather multipolar TER scattering driven by local field gradients.


Assuntos
Ouro , Análise Espectral Raman , Ouro/química , Piridinas/química
15.
Artigo em Inglês | MEDLINE | ID: mdl-36360910

RESUMO

The aromatic amino compound 5-amino-2-(trifluoromethyl)pyridine acts as an intermediate in the synthesis of pharmaceutical products. However, the toxicity profile of this compound is sparse and no related poisoning events have been reported. Here, we report the case of a 35-year-old man who inhaled 5-amino-2-(trifluoromethyl)pyridine at work. After inhalation, the patient rapidly developed symptoms such as dizziness, fatigue, nausea, vomiting, chest tightness, and loss of consciousness. After admission, methemoglobinemia, hemolytic anemia, acute renal failure, and toxic encephalopathy occurred. Symptoms improved significantly after intravenous treatment with a low dose of methylene blue. This revealed that 5-amino-2-(trifluoromethyl)pyridine is toxic to the human body and can be absorbed through the respiratory tract, resulting in methemoglobinemia and toxic encephalopathy; thus, caution should be taken in industrial production.


Assuntos
Anemia Hemolítica , Metemoglobinemia , Síndromes Neurotóxicas , Intoxicação , Masculino , Humanos , Adulto , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/tratamento farmacológico , Azul de Metileno , Anemia Hemolítica/tratamento farmacológico , Piridinas/toxicidade , Piridinas/uso terapêutico
16.
Science ; 378(6621): 779-785, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36395213

RESUMO

Carbon-hydrogen (C-H) functionalization of pyridines is a powerful tool for the rapid construction and derivatization of many agrochemicals, pharmaceuticals, and materials. Because of the inherent electronic properties of pyridines, selective meta-C-H functionalization is challenging. Here, we present a protocol for highly regioselective meta-C-H trifluoromethylation, perfluoroalkylation, chlorination, bromination, iodination, nitration, sulfanylation, and selenylation of pyridines through a redox-neutral dearomatization-rearomatization process. The introduced dearomative activation mode provides a diversification platform for meta-selective reactions on pyridines and other azaarenes through radical as well as ionic pathways. The broad scope and high selectivity of these catalyst-free reactions render these processes applicable for late-stage functionalization of drugs.


Assuntos
Isoquinolinas , Quinolinas , Hidrogênio/química , Quinolinas/química , Piridinas/química , Carbono/química
17.
Science ; 378(6621): 773-779, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36395214

RESUMO

Pyridine halogenation reactions are crucial for obtaining the vast array of derivatives required for drug and agrochemical development. However, despite more than a century of synthetic endeavors, halogenation processes that selectively functionalize the carbon-hydrogen bond in the 3-position of a broad range of pyridine precursors remain largely elusive. We report a reaction sequence of pyridyl ring opening, halogenation, and ring closing whereby the acyclic Zincke imine intermediates undergo highly regioselective halogenation reactions under mild conditions. Experimental and computational mechanistic studies indicate that the nature of the halogen electrophile can modify the selectivity-determining step. Using this method, we produced a diverse set of 3-halopyridines and demonstrated late-stage halogenation of complex pharmaceuticals and agrochemicals.


Assuntos
Halogenação , Iminas , Piridinas/química , Ligação de Hidrogênio
18.
Science ; 378(6621): 710-711, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36395229

RESUMO

Chemical reactions break a pyridine ring to allow its modification.


Assuntos
Piridinas
20.
Dalton Trans ; 51(45): 17263-17276, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36317406

RESUMO

In recent years, Ru(II) complexes have gained high importance in medicinal chemistry due to their significant anti-cancer activities, which are directly related to their DNA binding ability. In this report, the chemistry and cytotoxicity of two new Ru(II) complexes containing imidazole pyridine (Ru-1) and imidazole quinoline (Ru-2) have been studied. The prepared compounds were characterized using infrared (IR), nuclear magnetic resonance (NMR), mass spectrometry (MS), isothermal titration calorimetry (ITC), UV-Vis, and fluorescence spectral techniques. The structural analyses show that the Ru(II) complexes exhibit a 'piano stool' coordination geometry and they are composed of one bound arene, two sigma bonded benzil nitrogen atoms, and labile chlorine linked to Ru(II). The photo-physical properties of these complexes were examined, and they exhibit absorption peaks at 260 nm and 380 nm, which are due to the involvement of intra-ligand charge transitions (ILCT) and metal-to-ligand charge transitions (MLCT), respectively. The binding process of the Ru(II) complexes with DNA and BSA is non-covalent in nature and the binding constants of Ru-1 and Ru-2 complexes with DNA and BSA were found to be 1 × 105 M-1 and 1 × 103 M-1, respectively. In the presence of the Ru(II) complexes, ethidium bromide (EtBr) is competitively displaced from DNA by intercalation of the Ru(II) complexes in DNA and it is well corroborated by viscosity and in silico studies. Both the ligands and Ru(II) complexes were carefully investigated in vitro for cytotoxicity against HeLa, MCF-7, and MDA-MB-231 cells. Surprisingly, both Ru(II) complexes exhibit superior cytotoxicity to cisplatin with a low LD50 value against the examined cancer cells. Besides, an insignificant effect on HEK normal cells (LD50 > 140 µM) was observed.


Assuntos
Antineoplásicos , Complexos de Coordenação , Quinolinas , Rutênio , Humanos , Rutênio/química , Ligantes , Complexos de Coordenação/química , Estrutura Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , DNA/química , Imidazóis/farmacologia , Quinolinas/farmacologia , Piridinas/farmacologia , Linhagem Celular Tumoral
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