Otávio Chaves

University of Coimbra | UC · Department of Chemistry

We report the DNA-binding properties of three porphyrins with peripheral thienyl substituents (TThPor, PdTThPor and PtTThPor). The binding capacity of each porphyrin with DNA was determined by UV-Vis and steady-state fluorescence emission spectroscopy combined with molecular docking calculations. The results suggest that the interaction of these co...

We report the synthesis and characterization of new tri-cationic corrole derivatives, containing Pt(II) or Pd(II) complexes attached at the peripheral position of thienyl moieties. Corrole derivatives were characterized through microanalysis, electrochemical, spectrometry and spectroscopy analysis. Singlet and triplet excited-states are investigate...

Chalcone and thiosemicarbazone have attracted attention due to their easy synthetic procedure and high success in the development of antiviral and antitumor, however, there are few biological data on the evaluation of chalcone-thiosemicarbazone hybrids and their complexation with metal ions. In this sense, the present work reports the synthesis and...

The trans-A2B-corrole series was prepared starting with 5-(pentafluorophenyl)dipyrromethene, which was then reacted with respective aryl-substituted aldehyde by Gryko synthesis. It was further characterized by HRMS and electrochemical methods. In addition, we investigated experimental photophysical properties (absorption, emission by steady-state a...

Orally available antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary because of the continuous circulation of new variants that challenge immunized individuals. Because severe COVID-19 is a virus-triggered immune and inflammatory dysfunction, molecules endowed with both antiviral and anti-inflammatory activ...

Antibiotic resistance associated with pulmonary infection agents has become a public health problem, being considered one of the main priorities for immediate resolution. Thus, to increase the therapeutic options in the fight against resistant microorganisms, the synthesis of molecules from pre-existing drugs has shown to be a promising alternative...

Cancer and parasitic diseases, such as leishmaniasis and Chagas disease, share similarities that allow the co-development of new antiproliferative agents as a strategy to quickly track the discovery of new drugs. This strategy is especially interesting regarding tropical neglected diseases, for which chemotherapeutic alternatives are extremely outd...

With the increasing development of metallopharmaceuticals, coordination compounds become viable alternatives for therapeutic uses. Despite the importance of platinum derivatives in this area, first-row transition metals complexes are welcome due to their characteristics. Vanadium is a promising metal in this context, as it has a range of compounds...

The chymotrypsin-like cysteine protease (3CLpro, also known as main protease—Mpro) and papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been used as the main targets for screening potential synthetic inhibitors for posterior in vitro evaluation of the most promising compounds. In this sense, the pres...

Despite the fast development of vaccines, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still circulates through variants of concern (VoC) and escape the humoral immune response. SARS-CoV-2 has provoked over 200,000 deaths/months since its emergence and only a few antiviral drugs showed clinical benefit up to this moment. Thus, c...

The interaction between human serum albumin (HSA) and the non-charged synthetic photosensitizer 5,10,15,20-tetra(pyridine-4-yl)porphyrin (4-TPyP) was evaluated by in vitro assays under physiological conditions using spectroscopic techniques (UV-vis, circular dichroism, steady-state, time-resolved, synchronous, and 3D-fluorescence) combined with in...

Herpes simplex virus type-1 (HSV-1) infection causes several disorders and acyclovir is used as a reference compound. However, resistant strains are commonly observed. Herein, we in vestigate the effects of N-heterocyclic compounds (pyrazolopyridine derivatives) named ARA-04, ARA-05, and AM-57, towards the in vitro replication of HSV-1. We show tha...

Despite the fast development of vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still circulating and generating variants of concern (VoC) that escape the humoral immune response. In this context, the search for anti-SARS-CoV-2 compounds is still essential. A class of natural polyphenols known as flavonoids, frequently ava...

Helical complexes composed of organic ligand strands and metallic centers, called helicates, present interactions with biomacromolecules, such as deoxyribonucleic acid, as one of their main biological applications in bioinorganic chemistry. Despite the potential antineoplastic and antibacterial results of the interactions between helicates and biom...

The Front Cover shows the design of meso‐tetra‐(1‐pyrenyl)porphyrin derivatives, which interact with biomolecules. These porphyrins were fully characterized by photophysical and theoretical methods. The presence of metal species in the porphyrin core influences the ground and excited states. Biomolecule interaction experiments show that these porph...

A classical methodology to design free‐base meso ‐tetra‐(1‐pyrenyl)porphyrin ( H 2TPyrP ) and their corresponding metalloporphyrins containing Zn(II), Cu(II), Ni(II), Co(III), and Mn(III) was described. These porphyrins were characterized in terms of structure, photophysical, and interactions profile with calf‐thymus deoxyribonucleic acid (CT‐DNA)...

SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations of inhibitors of both the viral RNA-dependent RNA polymerase and the exonuclease could overcome this deficiency....

Despite the development of specific therapies against severe acute respiratory coronavirus 2 (SARS-CoV-2), the continuous investigation of the mechanism of action of clinically approved drugs could provide new information on the druggable steps of virus–host interaction. For example, chloroquine (CQ)/hydroxychloroquine (HCQ) lacks in vitro activity...

This study describes the synthesis, crystal structure, antioxidant activity, and molecular modeling calculations for two CuII complexes obtained from the condensation of ortho-vanillin with furfurylamine. Both complexes catalyzed superoxide dismutation and were evaluated and quantified by nitro blue tetrazolium photoreduction, efficiently demonstra...

The compound [Ru2O(keto)2(py)6](PF6)2, keto=ketoprofen and py=pyridine, interacts with calf thymus‐DNA with Kb=1.08×104 M−1. It efficiently quenches HSA fluorescence in different temperatures, with Ksv values in the 104–105 M−1 range, both by dynamic and static mechanisms. The data provided by the double logarithmic and van't Hoff approximations in...

We report the synthesis and characterization of two novel tetra-cationic porphyrins, containing Pt(II) or Pd(II) polypyridyl complexes attached at the peripheral position of N4-macrocycle. Compounds were characterized through elemental analysis, molar conductivity, cyclic voltammetry, and spectroscopy analysis. Photophysical and photobiological par...

Atazanavir (ATV) has already been considered as a potential repurposing drug to 2019 coronavirus disease (COVID-19); however, there are controversial reports on its mechanism of action and effectiveness as anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Through the pre-clinical chain of experiments: enzymatic, molecular docking,...

This manuscript describes the synthesis, structural analysis, antioxidant evaluation, cytotoxicity, interaction with DNA, and molecular docking modeling of copper(II) complexes derived from aromatic aldehydes and amines containing furyl and thiophene fragments (C1-C5). All compounds were tested as catalytic mimetics of superoxide dismutase (SOD) us...

Atazanavir (ATV) has already been considered as a potential repurposing drug to 2019 coronavirus disease (COVID-19), however, there are controversial reports on its mechanism of action and effectiveness as anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Through the pre-clinical chain of experiments: enzymatic, molecular docking,...

This work reports the synthesis of four homomolecular bis(n)-Lophines dyads achieved by a one-pot four component reaction. The dyads show absorption maxima below 300 nm and present intense fluorescence emission, with large Stokes shift, around 380 nm. Intercalation phenomenon and hydrophobic forces can be predicted for dyads, according to the resul...

This article presents the synthesis, characterization, evaluation of the mimetic potential of the catalytic activity of the superoxide dismutase enzyme, cytotoxic effects, evaluation of interactions with CT-DNA, and theoretical calculations of copper (II) mononuclear complexes. The C1, C2, and C3 complexes were obtained from the aldolic condensatio...

Anticoagulants are associated with clinical benefit against the 2019 coronavirus disease (COVID-19), preventing COVID-19 associated coagulopathy. Blood coagulation factor Xa (FXa) and SARS-CoV-2 major protease (Mpro) share over 80% homology at the three-dimensional protein level. Thus, it is worth interrogating whether there is crosstalk between in...

A novel curcumin analog namely 2-chloro-4,6-bis{(E)-3-methoxy-4-[(4-methoxybenzyl)oxy]-styryl}pyrimidine (compound 7) was synthesized by three-step reaction. The condensation reaction of protected vanillin with 2-chloro-4,6-dimethylpyrimidine (6) was the most efficient step, resulting in a total yield of 72%. The characterization of compound 7 was...

Phytochemical studies of Cespedesia spathulata (Ochnaceae) leaves using 1H, 13C NMR, and GC-MS have led to the isolation of some metabolites identified for the first time in these species such as cathechin, epicatechin, vitexin, orientin, 6''-O-acetyl-vitexin, sitosterol, stigmasterol, phytol, 4,5-dihydrovomifoliol and a mixture of aliphatic methyl...

Experimental, biophysical, and molecular modelling studies between25I-NBOHand25I-NBOMewith human serum albumin (HSA) have indicated that these recreational drugs simultaneously bind to site I and II of the protein, with25I-NBOMeshowing a greater affinity for the transport protein, and that both compounds were able to perturb the native structure of...

Two fluorinated corrole derivatives, namely H3MebpyCor and RuMebpyCor, were synthesized and characterized in terms of their photophysical, electrochemical, and photooxidation behavior. Their biomolecular binding capacity toward Human Serum Albumin (HSA) and calf thymus DNA (CT-DNA) was also evaluated. The experimental data were correlated with theo...

SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations of inhibitors of both the viral RNA-dependent RNA polymerase and the exonuclease could overcome this deficiency....

Fluoroquinolones are a family of broad spectrum, systemic antibacterial agents that have been used as therapy for infections in the respiratory and alimentary tract in animals. The pharmacodynamic of this class is widely described, predominantly to the commercial drugs ciprofloxacin (CIP), enrofloxacin (ENR), and pefloxacin (PEF). Bovine serum albu...

The ~ 2.4 µm long rhinovirus ss(+)RNA genome consists of roughly 7,200 nucleotides. It is tightly folded to fit into the ~ 22 nm diameter void in the protein capsid. In addition to previously predicted secondary structural elements in the RNA, using the QGRS mapper, we revealed the presence of multiple quadruplex forming G-rich sequences (QGRS) in...

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease, a neglected tropical disease that is endemic in Latin America and spreading worldwide due to globalization. The current treatments are based on benznidazole and nifurtimox; however, these drugs have important limitations and limited efficacy during the chronic phase, reinforcing...

Monosaccharides, e.g. fructose, glucose, and arabinose are present in most foods consumed daily, whether, in natural or industrialized forms, and their concentration in the human bloodstream can impact the formation of advanced glycation end-products (AGEs, prevalent in people with diabetes) impacting the profile of Human Serum Albumin (HSA) in bio...

Two new series of conjugated arylethenyl-1,3,4-oxadiazolyl-1,2,4-oxadiazoles were obtained and spectroscopically characterized in terms of UV-Vis absorption, fluorescence and interaction with CT-DNA and Human Serum Albumin (HSA) biomolecules. Phenyl- and 1-naphthyl-bearing examples were analysed, and the spectroscopic properties of its substitution...

Two fluorinated meso-C 6 F 5 -corroles (5,15-bis(pentafluorophenyl)-10-(phenyl)corrole and 5,15-bis(pentafluorophenyl)-10-(1-pyrenyl)corrole) were biologically evaluated in terms of binding affinity to human serum albumin (HSA) and calf-thymus DNA (CT-DNA) via multiple spectroscopic techniques under physiological conditions combined with molecular...

The free-base meso-tetra(4-pyridylvinylphenyl)porphyrin (1a) and its zinc(II) complex were synthesized and then functionalized with [Ru(bpy)2Cl]+ units (2a and 2b) via conventional methods and evaluated in terms of photophysical, electrochemical and biological aspects. All porphyrins present moderate singlet oxygen production and fluorescence quant...

This article deals with the synthesis of Schiff-based bis-azomethine-based ligands derived from pyridoxal and aliphatic dihydrazides and the synthesis of nickel(II) complexes C1–C4. The synthesized complexes had their structures elucidated by monocrystal X-ray diffraction and were characterized by vibrational and absorption spectroscopy. The synthe...

A series of 2-amino-1,4-naphthoquinone derivatives (NQA-NQF) was synthesized by alternative methods (ultrasonication and microwave irradiation), with yields ranging from 40 to 71%, and without the need of further recrystallization. Each compound was evaluated against four Gram-positive (Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureu...

The present work reports the spectroscopic and theoretical evaluation of the interaction between calf-thymus DNA (CT-DNA) and free-base meso-tetra-(ruthenated) porphyrin (H2RuTPyP) or its corresponding Zn(II) complex (ZnRuTPyP). Spectroscopic measurements (UV–vis, circular dichroism and steady-state fluorescence emission) combined with theoretical...

Synthesis of four compounds belonging to mesoionic class, (E)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (5a–d) and their biological evaluation against MT2 and C92 cell lines infected with human T-cell lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukemia/lymphoma (ATLL), and non-infected cell lin...

New isomeric tetra-cationic porphyrins containing peripheral [Pd(bpy)Cl]+ units attached at pyridyl substituents were synthetized and fully characterized. The porphyrins present an intense Soret band located in the blue spectral region and additional four weaker red-shifted Q bands in the visible spectral region (about 500-700 nm). The obtained Str...

The synthesis and structural characterization of novel platinum complexes ([PtII(Pz)2Cl2] – C1, C2 and C3) featuring diphenyl-pyrazole derived ligands: para-fluorophenyl and para-substituted phenyl (-CH3, -F and -Cl for L1, L2 and L3, respectively) were reported and it was also evaluated their potential antitumor activity. The elemental, molar cond...

The interaction between human serum albumin (HSA), the most abundant protein in the human circulatory system, and the potential anti-parasitic drug (E)-2-((6-iodobenzo[d][1,3]dioxol-5-yl)methylene)hydrazinecarbothioamide (6-IPTSC) was evaluated in vitro by spectroscopic techniques (circular dichroism, steady-state, time-resolved and synchronous flu...

Herein we report the synthesis of a series of amino acid-derived triazoles by an organocatalytic cycloaddition reaction between azides and carbonyl compounds, catalyzed by a simple amine. These compounds present absorption maxima located in the UV-B ascribed to fully spin and symmetry allowed electronic transitions and a main fluorescence emission...

The interaction between human serum albumin (HSA) and two porphyrin-based tetra-cationic photosensitizers were investigated via spectroscopic techniques (steady-state, time-resolved fluorescence and circular dichroism) combined to theoretical calculations (molecular docking). Similarities and differences in the binding behavior of a porphyrin beari...

This work presents the synthesis, characterization of copper(II) complexes (C1-C6) and the potential of these compounds to mimic the catalytic activity of the enzyme superoxide dismutase (SOD). The copper(II)complexes were obtained by reaction between the aldol condensation between substituted aromatic hydrazides and aromatic aldehydes (salicylic a...

A series of seven chalcone-thiosemicarbazones (5a–5g) were synthesized and evaluated as potential new drugs (anti-leishmanial effect). Although four of the chalcone-thiosemicarbazones are already known, none of them or any compound in this class has been previously investigated for their effects on parasites of the Leishmania genus. The compounds w...

Synthesis of dinuclear oxadiazole–adamantane platinum(II) and palladium(II) complexes (PtO, PdO) and mononuclear thiazolidine derivative complexes (PtT, PdT) was described. Characterization was performed by elemental analysis, infrared, UV–visible, ¹H, ¹³C, ¹⁹⁵Pt NMR spectra, MS spectroscopy and single crystal X-ray diffraction. The cytotoxicity by...

Thiosemicarbazone is a class of compounds with potential applications in medicine, presenting high capacity to inhibit the growth of cancer cells as well as low toxicity. Because of high interest in anticancer studies involving thiosemicarbazones as new chemotherapeutic agents, a synthetic thiosemicarbazone derivative, 4-N-(2′-methoxy-styryl)-thios...

Synthesis of three novel inorganic complexes (Zn(II), Pd(II), and Pt(II) – [Zn(H2L)](NO3)2, [Pd(L)], and [Pt(L)], respectively) based on 2,6-diformylpyridine-bis-(4-phenyl) thiosemicarbazone (H2L) was obtained under reflux medium, yielded in the range of 67% and 86%. Characterization of each compound was done via X-ray diffraction and spectroscopic...

The present work reports the interaction between human serum albumin (HSA) – the main bio-distributor of exogenous and endogenous compounds in the human bloodstream -and two synthetic Ru(II)-porphyrins (4-RuTPyP and 4-ZnRuTPyP), by multiple spectroscopic techniques (steady-state, time-resolved, circular dichroism, synchronous and 3D fluorescence) c...

The present study reports the biological evaluation of vanadium(V) complexes (1–3) against three different proteins: tyrosinase, acetylcholinesterase (AChE), and human serum albumin (HSA), which were studied by spectroscopic techniques and molecular docking. Despite the synthesis and characterization of complexes 1 and 2 having already previously d...

In the type II diabetes mellitus, Metformin hydrochloride is recommended as a common FAD approved drug. Synthesis of novel metformin series has been widely explored, mainly due to its biological importance and to improve their pharmacokinetic profile. Generally, human serum albumin (HSA) is the main protein used to study drug viability in vitro ana...

Chagas disease is a neglected tropical disease caused by the hemoflagellated parasite Trypanosoma cruzi (Kinetoplastida). The only available drug to treat chagasic patients in Brazil, the nitroheterocycle benznidazole, is effective solely during the acute phase of the infection. There is accordingly a need to develop new therapeutic tools for the t...

Based on our previous report, (2E)‐3‐(4‐bromophenyl)‐1‐(1H‐indol‐3‐yl) prop‐2‐en‐1‐one (IC9) showed potent and reversible hMAO−B inhibitor with Ki=0.010±0.005 μM and a selectivity index of 120 ‐ better than selegiline, the standard drug for hMAO−B. To continue the pharmacological investigation of IC9, the present study describes in vitro interactio...

The interaction between HSA and two semi-synthetic potential anti-cancer agents derived from trans-dehydrocrotonin-methyl-hydrazone (MHDCTN) and phenyl-hydrazone (PHDCTN) was evaluated under physiological conditions at 296, 303 and 310 K by multi-spectroscopic techniques and molecular docking calculations. Steady state fluorescence quenching indica...

The interaction between the main carrier of endogenous and exogenous compounds in the human bloodstream (human serum albumin, HSA) and a potential anticancer compound (the capsaicin analogue RPF101) was investigated by spectroscopic techniques (circular dichroism, steady-state, time-resolved, and synchronous fluorescence), zeta potential, and compu...

A series of N-aryl-2-phenyl-hydrazinecarbothioamides have been investigated as possible inhibitors of tyrosinase, an enzyme involved in the development of melanomas. The hydrazinecarbothioamides 1–6 were synthesized from the reaction between phenylhydrazine and isothiocyanates, for which three different methods have been employed, namely stirring a...