Search Results (7)

Background/Objectives: Leishmaniasis is one of the 20 Neglected Tropical Diseases according to the WHO, affecting approximately 12 million people in four continents, generating serious public health problems. The lack of therapeutic options, associated with toxicity and the emergence of resistance to the few available drugs, makes it urgent to develop new drug options. In this context, the aims of this work are to expand the knowledge about the pharmacophore group responsible for the antileishmanial potential of 2-aminothiophene derivatives. Thus, new compounds were synthesized containing chemical modifications at the C-3, C-4, and C-5 positions of the 2-aminothiophene ring, in addition to the S-Se bioisosterism. Methods: Dozens of 2-AT and 2-aminoselenophen (2-AS) derivatives were sequentially synthesized through applications of the Gewald reaction and were then evaluated in vitro for their activities against L. amazonensis and for cytotoxicity against macrophages. Results: Several series of compounds were synthesized, and it was possible to identify some substitution patterns favorable to the activity generating compounds with IC₅₀ values below 10 µM, such as the non-essentiality of the presence of a carbonitrile group at C-3; the importance of the presence and size of cycloalkyl/piperidinyl chains at C-4 and C-5 in modulating the activity; and the increase in activity without affecting the safety of the S/Se bioisosteric substitution. Conclusions: Taken together, these findings reaffirm the great potential of 2-aminothiophenes to generate antileishmanial drug candidates and offers contributions to the drug design of compounds with an even more promising profile for the problem of leishmaniasis. Full article

In this study, films of chitosan and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), a 2-aminothiophene derivative with great pharmacological potential, were prepared as a system for a topical formulation. 6CN-chitosan films were characterized by physicochemical analyses, such as Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electronic microscopy (SEM). Additionally, the antifungal potential of the films was evaluated in vitro against three species of Candida (C. albicans, C. tropicalis, and C. parapsilosis). The results of the FTIR and thermal analysis showed the incorporation of 6CN in the polymer matrix. In the diffractogram, the 6CN-chitosan films exhibited diffraction halos that were characteristic of amorphous structures, while the micrographs showed that 6CN particles were dispersed in the chitosan matrix, exhibiting pores and cracks on the film surface. In addition, the results of antifungal investigation demonstrated that 6CN-chitosan films were effective against Candida species showing potential for application as a new antifungal drug. Full article

The novel 2-aminothiophene derivative 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN) has shown potential anti-proliferative activity in human cancer cell lines. However, the poor aqueous solubility of 6CN impairs its clinical use. This work aimed to develop binary 6CN-β-cyclodextrin (βCD) systems with the purpose of increasing 6CN solubility in water and therefore, to improve its pharmacological activity. The 6CN-βCD binary systems were prepared by physical mixing, kneading and rotary evaporation methods and further characterized by FTIR, XRD, DSC, TG and SEM. In addition, molecular modeling and phase solubility studies were performed. Finally, MTT assays were performed to investigate the cytostatic and anti-proliferative effects of 6CN-βCD binary systems. The characterization results show evident changes in the physicochemical properties of 6CN after the formation of the binary systems with βCD. In addition, 6CN was associated with βCD in aqueous solution and the solid state, which was confirmed by molecular modeling and the aforementioned characterization techniques. Phase solubility studies indicated that βCD forms stable 1:1 complexes with 6CN. The MTT assay demonstrated the cytostatic and anti-proliferative activities of 6CN-βCD binary systems and therefore, these might be considered as promising candidates for new anticancer drugs. Full article

Different chemotypes are described as anti-inflammatory. Among them the N-acylhydrazones (NAH) are highlighted by their privileged structure nature, being present in several anti-inflammatory drug-candidates. In this paper a series of functionalized 3-aminothiophene-2-acylhydrazone derivatives 5a–i were designed, synthesized and bioassayed. These new derivatives showed great anti-inflammatory and analgesic potency and efficacy. Compounds 5a and 5d stand out in this respect, and were also active in CFA-induced arthritis in rats. After daily treatment for seven days with 5a and 5d (50 µmol/Kg), by oral administration, these compounds were not renal or hepatotoxic nor immunosuppressive. Compounds 5a and 5d also displayed good drug-scores and low risk toxicity calculated in silico using the program OSIRIS Property Explorer. Full article

The crystal and molecular structures of two 2-aminothiophene derivatives, potential allosteric enhancers at the human A₁ adenosine receptor, are reported. (2-Amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)(phenyl)methanone (1) crystallizes in the orthorhombic space group Pna2₁ (a = 9.2080(4) Å, b = 14.0485(7) Å, c = 10.3826(6) Å), and (2-amino-5-ethylthiophen-3-yl)(2-chlorophenyl)methanone (2) crystalizes in the monoclinic P2₁/c space group with unit cell parameters a = 10.6092(8) Å, b = 10.8355(8) Å, c = 11.1346(9) Å, β = 98.643(6)Å. In both molecules the intramolecular N–H···O=C hydrogen bonds close six-membered planar rings and significantly influence the molecular conformation. Intermolecular N–H···O bonds connect the molecules in infinite chains along a in case of 1, and along b in 2; in each case the appropriate unit cell axis is approximately 10 Å long. Full article

Fifty 2-[(arylidene)amino]-4,5-cycloalkyl[b]thiophene-3-carbonitrile derivatives were screened for their in vitro antifungal activities against Candida krusei and Cryptococcus neoformans. Based on experimentally determined minimum inhibitory concentration (MIC) values, we conducted computer-aided drug design studies [molecular modelling, chemometric tools (CPCA, PCA, PLS) and QSAR-3D] that enable the prediction of three-dimensional structural characteristics that influence the antifungal activities of these derivatives. These predictions provide direction with regard to the syntheses of new derivatives with improved biological activities, which can be used as therapeutic alternatives for the treatment of fungal infections. Full article

Synthesis, isomerisation and structure elucidation of the title compounds 1–6 and its isomers 7–12 by FTIR, ¹H, ¹³C, ¹⁵N, ⁷⁷Se NMR spectroscopy is reported. Ethyl 2–(3–acylselenoureido)thiophene–3–carboxylates and their benzoanalogues (where acyl is benzoyl and pivaloyl) were prepared by addition of ethyl 2–aminothiophene–3–carboxylates and ethyl 2–aminobenzoate on benzoyl– or pivaloylisoselenocyanate in acetone solution. An isomerization of 1–6 to the corresponding 3–acylisoselenoureas 7–12 was obtained. The isomerisation proceeds either by irradiation with light (340–400 nm) or in the case of benzoylderivatives 1, 3, 5 by treatment with acetic acid. On the other hand the acid action in the pivaloyl set inhibited this isomerisation and evoked the retroisomerisation reaction of 8, 10, 12 to 2, 4, 6. Thermal analyses showed that isomerisation can be initiated also by heating. These changes proceed in the solid phase as an exothermic process at an elevated temperature but always below the temperature of melting. The structure 2 was supported by X–ray analysis. Molecular design of 2 and 8 was modeled during application of ab initio quantum chemistry calculation. Full article