Synthesis of 3,4-Disubstituted Maleimide Derivatives via Phosphine-Catalyzed Isomerization of α-Succinimide-Substituted Allenoates Cascade γ'-Addition with Aryl Imines.

3,4-disubstituted maleimides find wide applications in various pharmacologically active compounds. This study presents a highly effective approach for synthesizing derivatives of 3,4-disubstituted maleimides through the direct isomerization of α-succinimide-substituted allenoates, followed by a cascade γ'-addition and aryl imines using PR3 as a catalyst. The resulting series of 3,4-disubstituted maleimides exhibited excellent stereoselectivities, achieving yields of up to 86%. To our knowledge, the phosphine-mediated γ'-addition reaction of allenoates is seldom reported.

General skin and nasal decolonization with octenisan® set before and after elective orthopedic surgery in selected patients at elevated risk for revision surgery and surgical site infections-a single-center, unblinded, superiority, randomized controlled trial (BALGDEC trial).

BACKGROUND: The preoperative body surface and nasal decolonization may reduce the risk of surgical site infections (SSI) but yields conflicting results in the current orthopedic literature. METHODS: We perform a single-center, randomized-controlled, superiority trial in favor of the preoperative decolonization using a commercial product (octenidine® set). We will randomize a total number of 1000 adult elective orthopedic patients with a high risk for SSI and/or wound complications (age ≥ 80 years, chronic immune-suppression, American Society of Anesthesiologists score 3-4 points) between a decolonization (octenisan® wash lotion 1 × per day and octenisan® md nasal gel 2-3 × per day; during 5 days) and no decolonization. Decolonized patients will additionally fill a questionnaire regarding the practical difficulties, the completeness, and the adverse events of decolonization. The primary outcomes are SSI and revision surgeries for postoperative wound problems until 6 weeks postoperatively (or 1 year for surgeries with implants or bone). Secondary outcomes are unplanned revision surgeries for non-infectious problems and all adverse events. With 95% event-free surgeries in the decolonization arm versus 90% in the control arm, we formally need 2 × 474 elective orthopedic surgeries included during 2 years. DISCUSSION: In selected adult orthopedic patients with a high risk for SSI, the presurgical decolonization may reduce postoperative wound problems, including SSI. TRIAL REGISTRATION: ClinicalTrial.gov NCT05647252. Registered on 9 December 2022. PROTOCOL VERSION: 2 (5 December 2022).

Synthesis of novel aryl-substituted 2-aminopyridine derivatives by the cascade reaction of 1,1-enediamines with vinamidinium salts to develop novel anti-Alzheimer agents.

Alzheimer's disease (AD), a severe neurodegenerative disorder, imposes socioeconomic burdens and necessitates innovative therapeutic strategies. Current therapeutic interventions are limited and underscore the need for novel inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), enzymes implicated in the pathogenesis of AD. In this study, we report a novel synthetic strategy for the generation of 2-aminopyridine derivatives via a two-component reaction converging aryl vinamidinium salts with 1,1-enediamines (EDAMs) in a dimethyl sulfoxide (DMSO) solvent system, catalyzed by triethylamine (Et3N). The protocol introduces a rapid, efficient, and scalable synthetic pathway, achieving good to excellent yields while maintaining simplistic workup procedures. Seventeen derivatives were synthesized and subsequently screened for their inhibitory activity against AChE and BChE. The most potent derivative, 3m, exhibited an IC50 value of 34.81 ± 3.71 µM against AChE and 20.66 ± 1.01 µM against BChE compared to positive control donepezil with an IC50 value of 0.079 ± 0.05 µM against AChE and 10.6 ± 2.1 µM against BChE. Also, detailed kinetic studies were undertaken to elucidate their modes of enzymatic inhibition of the most potent compounds against both AChE and BChE. The promising compound was then subjected to molecular docking and dynamics simulations, revealing significant binding affinities and favorable interaction profiles against AChE and BChE. The in silico ADMET assessments further determined the drug-like properties of 3m, suggesting it as a promising candidate for further pre-clinical development.

Synthesis and Antioxidant Activity of N-Benzyl-2-[4-(aryl)-1H-1,2,3-triazol-1-yl]ethan-1-imine Oxides.

The synthesis, antioxidant capacity, and anti-inflammatory activity of four novel N-benzyl-2-[4-(aryl)-1H-1,2,3-triazol-1-yl]ethan-1-imine oxides 10a-d are reported herein. The nitrones 10a-d were tested for their antioxidant properties and their ability to inhibit soybean lipoxygenase (LOX). Four diverse antioxidant tests were used for in vitro antioxidant assays, namely, interaction with the stable free radical DPPH (1,1-diphenyl-2-picrylhydrazyl radical) as well as with the water-soluble azo compound AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride), competition with DMSO for hydroxyl radicals, and the scavenging of cationic radical ABTS•+ (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation). Nitrones 10b, 10c, and 10d, having the 4-fluorophenyl, 2,4-difluorophenyl, and 4-fluoro-3-methylphenyl motif, respectively, exhibited high interaction with DPPH (64.5-81% after 20 min; 79-96% after 60 min), whereas nitrone 10a with unfunctionalized phenyl group showed the lowest inhibitory potency (57% after 20 min, 78% after 60 min). Nitrones 10a and 10d, decorated with phenyl and 4-fluoro-3-methylphenyl motif, respectively, appeared the most potent inhibitors of lipid peroxidation. The results obtained from radical cation ABTS•+ were not significant, since all tested compounds 10a-d showed negligible activity (8-46%), much lower than Trolox (91%). Nitrone 10c, bearing the 2,4-difluorophenyl motif, was found to be the most potent LOX inhibitor (IC50 = 10 µM).

Pt(II) Bis(pyrrole-imine) complexes: Luminescent probes and cytotoxicity in MCF-7 cells†.

Four Pt(II) bis(pyrrole-imine) Schiff base chelates (1-4) were synthesised by previously reported methods, through a condensation reaction, and the novel crystal structure of 2,2'-{propane-1,3-diylbis[nitrilo(E)methylylidene]}bis(pyrrol-1-ido)platinum(II) (1) was obtained. Pt(II) complexes 1-4 exhibited phosphorescence, with increased luminescence in anaerobic solvents or when bound to human serum albumin (HSA). One of the complexes shows a 15.6-fold increase in quantum yield when bound to HSA and could be used to detect HSA concentrations as low as 5 nM. Pt(II) complexes 1-3 was investigated as potential theranostic agents in MCF-7 breast cancer cells, but only complex 3 exhibited cytotoxicity when irradiated with UV light (λ355nmExcitation). Interestingly, the cytotoxicity of complex 1 was unresponsive to UV light irradiation. This indicates that only complex 3 can be considered a potential photosensitising agent.

High-Performance Trimethylamine Sensor Based on an Imine Covalent Organic Framework.

As trimethylamine (TMA) is widely used in agriculture and industry, inhalation of TMA can cause very serious negative effects on human health. However, most of the current gas sensors for detecting TMA are commonly performed at high temperatures and cannot meet market needs. Inspired by this, we prepared imine covalent organic frameworks (TB-COF) synthesized from two monomers, 1,3,5-tris(4-aminophenyl)benzene (TAPB) and 1,3,5-benzotricarboxaldehyde (BTCA), using acetic acid as a catalyst at room temperature. Based on this, three sensors were prepared for gas sensitivity testing, namely, TA, BT, and TB-COF sensors. The three sensors were tested for 15 different gases at room temperature. From the whole gas sensitivity data, the TB-COF sensor made by compositing TA and BT has a higher sensitivity (6845.9%) to TMA at 500 ppm, which is 6.1 and 5.4 times higher than the response of TA and BT sensors, respectively. The TB-COF sensor adsorbs and desorbs TMA in a controlled 23 s cycle with a low detection limit of 28.6 ppb. This result indicates that TB-COF prepared at room temperature can be used as a gas-sensitive sensing material for real-time monitoring of TMA. The gas sensing results demonstrate the great potential of COFs for sensor development and application and provide ideas for further development of COFs-based gas sensors.

Engineered Imine Reductase for Asymmetric Synthesis of Dextromethorphan Key Intermediate.

(S)-1-(4-Methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline ((S)-1-(4-methoxybenzyl)-OHIQ) is the key intermediate of the nonopioid antitussive dextromethorphan. In this study, (S)-IR61-V69Y/P123A/W179G/F182I/L212V (M4) was identified with a 766-fold improvement in catalytic efficiency compared with wide-type IR61 through enzyme engineering. M4 could completely convert 200 mM of 1-(4-methoxybenzyl)-3,4,5,6,7,8-hexahydroisoquinoline into (S)-1-(4-methoxybenzyl)-OHIQ in 77% isolated yield, with >99% enantiomeric excess and a high space-time yield of 542 g L-1 day-1, demonstrating a great potential for the synthesis of dextromethorphan intermediate in industrial applications.

Simultaneous determination of trace marine lipophilic and hydrophilic phycotoxins in various environmental and biota matrices.

An efficient and sensitivity approach, which combines solid-phase extraction or ultrasonic extraction for pretreatment, followed by ultra-performance liquid chromatography-tandem mass spectrometry, has been established to simultaneously determine eight lipophilic phycotoxins and one hydrophilic phycotoxin in seawater, sediment and biota samples. The recoveries and matrix effects of target analytes were in the range of 61.6-117.3 %, 55.7-121.3 %, 57.5-139.9 % and 82.6 %-95.0 %, 85.8-106.8 %, 80.7 %-103.3 % in seawater, sediment, and biota samples, respectively. This established method revealed that seven, six and six phycotoxins were respectively detected in the Beibu Gulf, with concentrations ranging from 0.14 ng/L (okadaic acid, OA) to 26.83 ng/L (domoic acid, DA) in seawater, 0.04 ng/g (gymnodimine-A, GYM-A) to 2.75 ng/g (DA) in sediment and 0.01 ng/g (GYM-A) to 2.64 ng/g (domoic acid) in biota samples. These results suggest that the presented method is applicable for the simultaneous determination of trace marine lipophilic and hydrophilic phycotoxins in real samples.

Asymmetric hydrogenation of ketimines with minimally different alkyl groups.

Asymmetric catalysis enables the synthesis of optically active compounds, often requiring the differentiation between two substituents on prochiral substrates1. Despite decades of development of mainly noble metal catalysts, achieving differentiation between substituents with similar steric and electronic properties remains a notable challenge2,3. Here we introduce a class of Earth-abundant manganese catalysts for the asymmetric hydrogenation of dialkyl ketimines to give a range of chiral amine products. These catalysts distinguish between pairs of minimally differentiated alkyl groups bound to the ketimine, such as methyl and ethyl, and even subtler distinctions, such as ethyl and n-propyl. The degree of enantioselectivity can be adjusted by modifying the components of the chiral manganese catalyst. This reaction demonstrates a wide substrate scope and achieves a turnover number of up to 107,800. Our mechanistic studies indicate that exceptional stereoselectivity arises from the modular assembly of confined chiral catalysts and cooperative non-covalent interactions between the catalyst and the substrate.

Innovative On-DNA Synthesis of Sulfides and Sulfoximines: Enriching the DEL Synthesis Toolbox.

DNA-encoded library (DEL) technologies enable the fast exploration of gigantic chemical space to identify ligands for the target protein of interest and have become a powerful hit finding tool for drug discovery projects. However, amenable DEL chemistry is restricted to a handful of reactions, limiting the creativity of drug hunters. Here, we describe a new on-DNA synthetic pathway to access sulfides and sulfoximines. These moieties, usually contemplated as challenging to achieve through alkylation and oxidation, can now be leveraged in routine DEL selection campaigns.

Copper(I)-nitrene platform for chemoproteomic profiling of methionine.

Methionine plays a critical role in various biological and cell regulatory processes, making its chemoproteomic profiling indispensable for exploring its functions and potential in protein therapeutics. Building on the principle of rapid oxidation of methionine, we report Copper(I)-Nitrene Platform for robust, and selective labeling of methionine to generate stable sulfonyl sulfimide conjugates under physiological conditions. We demonstrate the versatility of this platform to label methionine in bioactive peptides, intact proteins (6.5-79.5 kDa), and proteins in complex cell lysate mixtures with varying payloads. We discover ligandable proteins and sites harboring hyperreactive methionine within the human proteome. Furthermore, this has been utilized to profile oxidation-sensitive methionine residues, which might increase our understanding of the protective role of methionine in diseases associated with elevated levels of reactive oxygen species. The Copper(I)-Nitrene Platform allows labeling methionine residues in live cancer cells, observing minimal cytotoxic effects and achieving dose-dependent labeling. Confocal imaging further reveals the spatial distribution of modified proteins within the cell membrane, cytoplasm, and nucleus, underscoring the platform's potential in profiling the cellular interactome.

Efficacy assessment of novel methanimine derivatives in chronic constriction injury-induced neuropathic model: An in-vivo, ex-vivo and In-Silico approach.

The multicomponent etiology, complex clinical implications, dose-based side effect and degree of pain mitigation associated with the current pharmacological therapy is incapable in complete resolution of chronic neuropathic pain patients which necessitates the perpetual requirement of novel medication therapy. Therefore, this study explored the ameliorative aptitude of two novel methanimine imitative like (E)-N-(4-nitrobenzylidene)-4­chloro-2-iodobenzamine (KB 09) and (E)-N-(4-methylbenzylidene)-4­chloro-2-iodobenzamine (KB 10) in chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rat model. Standard behavioral tests like dynamic and static allodynia, cold, thermal and mechanical hyperalgesia along with rotarod activity were performed at various experimental days like 0, 3, 7, 14 and 21. Enzyme linked immunosorbent assay (ELISA) on spinal tissue and antioxidant assays on sciatic nerve were executed accompanied by molecular docking and simulation studies. Prolonged ligation of sciatic nerve expressively induced hyperalgesia as well as allodynia in rats. KB 09 and KB 10 substantially attenuated the CCI elicited hyperalgesia and allodynia. They significantly reduced the biomarkers of pain and inflammation like Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in ELISA and while enhanced the GSH, SOD and CAT and diminished the MDA levels during antioxidant assays. KB 09 displayed -9.62 kcal/mol with TNF-α and -7.68 kcal/mol binding energy with IL-6 whereas KB 10 exhibited binding energy of -8.20 kcal/mol with IL-6 while -11.68 kcal/mol with TNF-α and hence both trial compounds ensured stable interaction with IL-6 and TNF-α during computational analysis. The results advocated that both methanimine derivatives might be novel candidates for attenuation of CCI-induced neuropathic pain prospects via anti-nociceptive, anti-inflammatory and antioxidant mechanisms.

Identification and fungicides sensitivity evaluation of the causal agent of cobweb disease on Lyophyllum decastes in China.

BACKGROUND: Cobweb disease is a fungal disease that commonly affects the cultivation and production of edible mushrooms, leading to serious yield and economic losses. It is considered a major fungal disease in the realm of edible mushrooms. The symptoms of cobweb disease were found during the cultivation of Lyophyllum decastes. This study aimed to identify the causative pathogen of cobweb disease and evaluate effective fungicides, providing valuable insights for field control and management of L. decastes cobweb disease. RESULTS: The causal agent of cobweb disease was isolated from samples infected and identified as Cladobotryum mycophilum based on morphological and cultural characteristics, as well as multi-locus phylogeny analysis (ITS, RPB1, RPB2, and TEF1-α). Pathogenicity tests further confirmed C. mycophilum as the responsible pathogen for this condition. Among the selected fungicides, Prochloraz-manganese chloride complex, Trifloxystrobin, tebuconazole, and Difenoconazole exhibited significant inhibitory effects on the pathogen's mycelium, with EC50 values of 0.076 µg/mL, 0.173 µg/mL, and 0.364 µg/mL, respectively. These fungicides can serve as references for future field control of cobweb disease in L. decastes. CONCLUSION: This study is the first report of C. mycophilum as the causing agent of cobweb disease in L. decastes in China. Notably, Prochloraz-manganese chloride complex demonstrated the strongest inhibitory efficacy against C. mycophilum.

Octenidine exposure was not associated with reduced octenidine susceptibility of meticillin-resistant Staphylococcus aureus in an extended-care facility in Singapore.

OBJECTIVES: Antiseptics such as chlorhexidine gluconate (CHG) and octenidine dihydrochloride (OCT) are frequently used in hospitals to prevent and control the transmission of meticillin-resistant Staphylococcus aureus (MRSA). Given the increasing prevalence of reduced CHG susceptibility of MRSA, there are concerns about the possibility of reduced OCT susceptibility. This study evaluated the prevalence of reduced CHG and OCT susceptibility over 3 years, and assessed the association between OCT exposure and reduced OCT susceptibility in MRSA. METHODS: MRSA isolates from inpatients who acquired MRSA in an extended-care facility between 2019 and 2021 were included in antiseptic susceptibility testing. Inpatients were exposed to universal daily CHG bathing from January to September 2019, and universal daily OCT bathing after October 2019. The minimum inhibitory concentrations (MICs) of CHG and OCT were determined using the broth microdilution method. Multi-variable logistic regression was used to assess if OCT exposure was independently associated with reduced OCT susceptibility. RESULTS: Of 186 isolates, 179 (96%) had reduced CHG susceptibility (MIC ≥4 mg/L) and 46 (25%) had reduced OCT susceptibility (MIC ≥2 mg/L). Reduced OCT susceptibility rates were 26.9%, 13.8% and 14.3% in 2019, 2020 and 2021, respectively. Reduced CHG susceptibility rates were 95.4%, 100% and 95.9% in 2019, 2020 and 2021, respectively. OCT exposure was not associated with reduced OCT susceptibility (adjusted odds ratio 0.23, 95% confidence interval 0.08-0.75; P=0.014), after adjusting for age, gender, race, year of sample collection, days at risk in facility, hospitalization in preceding year, and MRSA colonization/infection in preceding year. CONCLUSION: The prevalence of reduced OCT susceptibility has remained low, despite universal OCT bathing for extended inpatient care. However, the rate of reduced CHG susceptibility was high. OCT exposure was not associated with reduced OCT susceptibility in MRSA.

A triple cysteine motif as major determinant of the modulation of neuronal KV7 channels by the paracetamol metabolite N-acetyl-p-benzo quinone imine.

BACKGROUND AND PURPOSE: The analgesic action of paracetamol involves KV7 channels, and its metabolite N-acetyl-p-benzo quinone imine (NAPQI), a cysteine modifying reagent, was shown to increase currents through such channels in nociceptors. Modification of cysteine residues by N-ethylmaleimide, H2O2, or nitric oxide has been found to modulate currents through KV7 channels. The study aims to identify whether, and if so which, cysteine residues in neuronal KV7 channels might be responsible for the effects of NAPQI. EXPERIMENTAL APPROACH: To address this question, we used a combination of perforated patch-clamp recordings, site-directed mutagenesis, and mass spectrometry applied to recombinant KV7.1 to KV7.5 channels. KEY RESULTS: Currents through the cardiac subtype KV7.1 were reduced by NAPQI. Currents through all other subtypes were increased, either by an isolated shift of the channel voltage dependence to more negative values (KV7.3) or by such a shift combined with increased maximal current levels (KV7.2, KV7.4, KV7.5). A stretch of three cysteine residues in the S2-S3 linker region of KV7.2 was necessary and sufficient to mediate these effects. CONCLUSION AND IMPLICATION: The paracetamol metabolite N-acetyl-p-benzo quinone imine (NAPQI) modifies cysteine residues of KV7 subunits and reinforces channel gating in homomeric and heteromeric KV7.2 to KV7.5, but not in KV7.1 channels. In KV7.2, a triple cysteine motif located within the S2-S3 linker region mediates this reinforcement that can be expected to reduce the excitability of nociceptors and to mediate antinociceptive actions of paracetamol.

Dendritic Pyridine-Imine Copper Complexes as Metallo-Drugs.

Since the discovery of cisplatin in the 1960s, the search for metallo-drugs that are more efficient than platinum complexes with negligible side effects has attracted much interest. Among the other metals that have been examined for potential applications as anticancer agents is copper. The interest in copper was recently boosted by the discovery of cuproptosis, a recently evidenced form of cell death mediated by copper. However, copper is also known to induce the proliferation of cancer cells. In view of these contradictory results, there is a need to find the most suitable copper chelators, among which Schiff-based derivatives offer a wide range of possibilities. Gathering several metal complexes in a single, larger entity may provide enhanced properties. Among the nanometric objects suitable for such purpose are dendrimers, precisely engineered hyperbranched macromolecules, which are outstanding candidates for improving therapy and diagnosis. In this review article, we present an overview of the use of a particular Schiff base, namely pyridine-imine, linked to the surface of dendrimers, suitable for complexing copper, and the use of such dendrimer complexes in biology, in particular against cancers.

Inhibition of superoxide and iNOS augment cutaneous nitric oxide-dependent vasodilation in non-Hispanic black young adults.

We assessed the combined effect of superoxide and iNOS inhibition on microvascular function in non-Hispanic Black and non-Hispanic White participants (n = 15 per group). Participants were instrumented with four microdialysis fibers: (1) lactated Ringer's (control), (2) 10 µM tempol (superoxide inhibition), (3) 0.1 mM 1400 W (iNOS inhibition), (4) tempol + 1400 W. Cutaneous vasodilation was induced via local heating and NO-dependent vasodilation was quantified. At control sites, NO-dependent vasodilation was lower in non-Hispanic Black (45 ± 9% NO) relative to non-Hispanic White (79 ± 9% NO; p < 0.01; effect size, d = 3.78) participants. Tempol (62 ± 16% NO), 1400 W (78 ± 12% NO) and tempol +1400 W (80 ± 13% NO) increased NO-dependent vasodilation in non-Hispanic Black participants relative to control sites (all p < 0.01; d = 1.22, 3.05, 3.03, respectively). The effect of 1400 W (p = 0.04, d = 1.11) and tempol +1400 W (p = 0.03, d = 1.22) was greater than tempol in non-Hispanic Black participants. There was no difference between non-Hispanic Black and non-Hispanic White participants at 1400 W or tempol + 1400 W sites. These data suggest iNOS has a greater effect on NO-dependent vasodilation than superoxide in non-Hispanic Black participants.

The Cyclic Imine Core Common to the Marine Macrocyclic Toxins Is Sufficient to Dictate Nicotinic Acetylcholine Receptor Antagonism.

Macrocyclic imine phycotoxins are an emerging class of chemical compounds associated with harmful algal blooms and shellfish toxicity. Earlier binding and electrophysiology experiments on nAChR subtypes and their soluble AChBP surrogates evidenced common trends for substantial antagonism, binding affinities, and receptor-subtype selectivity. Earlier, complementary crystal structures of AChBP complexes showed that common determinants within the binding nest at each subunit interface confer high-affinity toxin binding, while distinctive determinants from the flexible loop C, and either capping the nest or extending toward peripheral subsites, dictate broad versus narrow receptor subtype selectivity. From these data, small spiroimine enantiomers mimicking the functional core motif of phycotoxins were chemically synthesized and characterized. Voltage-clamp analyses involving three nAChR subtypes revealed preserved antagonism for both enantiomers, despite lower subtype specificity and binding affinities associated with faster reversibility compared with their macrocyclic relatives. Binding and structural analyses involving two AChBPs pointed to modest affinities and positional variability of the spiroimines, along with a range of AChBP loop-C conformations denoting a prevalence of antagonistic properties. These data highlight the major contribution of the spiroimine core to binding within the nAChR nest and confirm the need for an extended interaction network as established by the macrocyclic toxins to define high affinities and marked subtype specificity. This study identifies a minimal set of functional pharmacophores and binding determinants as templates for designing new antagonists targeting disease-associated nAChR subtypes.

Influence of diimine bidentate ligand in the nitrosyl and nitro terpyridine ruthenium complex on the HSA/DNA interaction and antiviral activity.

Nitric oxide (NO) acts in different physiological processes, such as blood pressure control, antiparasitic activities, neurotransmission, and antitumor action. Among the exogenous NO donors, ruthenium nitrosyl/nitro complexes are potential candidates for prodrugs, due to their physicochemical properties, such as thermal and physiological pH stability. In this work, we proposed the synthesis and physical characterization of the new nitro terpyridine ruthenium (II) complexes of the type [RuII(L)(NO2)(tpy)]PF6 where tpy = 2,2':6',2″-terpyridine; L = 3,4-diaminobenzoic acid (bdq) or o-phenylenediamine (bd) and evaluation of influence of diimine bidentate ligand NH.NHq-R (R = H or COOH) in the HSA/DNA interaction as well as antiviral activity. The interactions between HSA and new nitro complexes [RuII(L)(NO2)(tpy)]+ were evaluated. The Ka values for the HSA-[RuII(bdq)(NO2)(tpy)]+ is 10 times bigger than HSA-[RuII(bd)(NO2)(tpy)]+. The sites of interaction between HSA and the complexes via synchronous fluorescence suppression indicate that the [RuII(bdq)(NO2)(tpy)]+ is found close to the Trp-241 residue, while the [RuII(bd)(NO2)(tpy)]+ complex is close to Tyr residues. The interaction with fish sperm fs-DNA using direct spectrophotometric titration (Kb) and ethidium bromide replacement (KSV and Kapp) showed weak interaction in the system fs-DNA-[RuII(bdq)(NO)(tpy)]+. Furthermore, fs-DNA-[RuII(bd)(NO2)(tpy)]+ and fs-DNA-[RuII(bd)(NO)(tpy)]3+ system showed higher intercalation constant. Circular dichroism spectra for fs-DNA-[RuII(bd)(NO2)(tpy)]+ and fs-DNA-[RuII(bd)(NO)(tpy)]3+, suggest semi-intercalative accompanied by major groove binding interaction modes. The [RuII(bd)(NO2)(tpy)]+ and [RuII(bd)(NO)(tpy)]3+ inhibit replication of Zika and Chikungunya viruses based in the nitric oxide release under S-nitrosylation reaction with cysteine viral.