Vinícius R. Campos

Synthesis, antitubercular activity, and SAR study of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides

Tuberculosis treatment remains a challenge that requires new antitubercular agents due to the emergence of multidrug-resistant Mycobacterium strains. This paper describes the synthesis, the antitubercular activity and the theoretical analysis of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides (8a-b, 8e-f, 8i-j and 8n-o) and new analogues (8c-d, 8g-h, 8l-m and 8p-q). These derivatives were synthesized in good yields and some of them showed a promising antitubercular profile. Interestingly the N-acylhydrazone (NAH) 8n was the most potent against the Mycobacterium tuberculosis H37Rv strain (MIC=2.5 μg/mL) similar to or better than the current drugs on the market. The theoretical structure-activity relationship study suggested that the presence of the furyl ring and the electronegative group (NO(2)) as well as low lipophilicity and small volume group at R position are important structural features for the antitubercular profile of these molecules. NMR spectra, IR spectra and elemental analyses of these substances are reported.

Synthesis of carbohydrate-based naphthoquinones and their substituted phenylhydrazono derivatives as anticancer agents

A novel series of carbohydrate-based 1,2-naphthoquinones 13a–c and their substituted phenylhydrazono derivatives 14a–l were synthesized and evaluated for cytotoxicity against HL-60, MDA-MB435, HCT-116 and SF-295 cancer cell lines. The compounds 9a–c showed the best cytotoxicity profile (IC50 below 2 μM) against HL-60 and MDA-MB 435 human cells, while the hydrazone derivative 14i (IC50 HL-60 1.65 μM) was selective for leukemia when compared to the reference drug doxorubicin. None of the compounds exhibited lytic effects against mouse erythrocytes. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques (1H, 13C-APT, COSY-1H × 1H and HETCOR 1JCH) and by elemental analysis.

Synthesis and antimicrobial evaluation of promising 7-arylamino-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylates and their halogenated amino compounds for treating Gram-negative bacterial infections

Pathogenic bacteria may cause serious infections, such as pneumonia, which can be fatal especially to immunosuppressed individuals. Hospitalized patients are particularly susceptible to antibiotic-resistant infections, which are worsened when caused by resistant Gram-negative pathogens due to there being few therapeutic options available. Thus, this work describes the synthesis and in vitro antimicrobial profile of 7-arylamino-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylates and their halogenated aminoquinones against Gram-positive and Gram-negative bacteria. Interestingly, these bioactive substances have shown promising activity against Gram-negative pathogenic strains. Among these derivatives, two non-halogenated amino compounds exhibited promising MIC and MBC values (MIC = MBC = 1–2 μg mL−1) against Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853, two Gram-negative strains of clinical importance. In addition, mono- and di-brominated aminoquinones were also effective in preventing the growth of E. coli (MIC = MBC = 2–4 μg mL−1). The in vitro hemocompatibility evaluation showed a low toxicity profile for the active aminoquinones in hemolysis assays. These results suggest that these substances have potential for exploring the design of new antimicrobial prototypes against Gram-negative bacteria.

Synthesis of a new class of naphthoquinone glycoconjugates and evaluation of their potential as antitumoral agents

A novel series of carbohydrate-based naphthoquinones was synthesized and evaluated for cytotoxicity against different cancer cell lines. The compounds derived from 5-hydroxy-1,4-naphthoquinone (juglone) showed better cytotoxicity profiles against HCT-116, A-549 and MDA-MB 435 human cancer cells than the parent compound. The results suggest that the hydroxyl group on the aromatic ring increased the pro-oxidant activity of these new naphthoquinone derivatives. Furthermore, two derivatives were found to be more active against melanoma cells (MDA-MB435) than the clinically useful anticancer agent doxorubicin, and none of the compounds caused mouse erythrocyte lysis.

A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones.

Summary A new and efficient method for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones in one step with high yields from the reaction of lawsone with 1,3,5-triazinanes was developed.

Antivenom effects of 1,2,3-triazoles against Bothrops jararaca and Lachesis muta snakes.

Snake venoms are complex mixtures of proteins of both enzymes and nonenzymes, which are responsible for producing several biological effects. Human envenomation by snake bites particularly those of the viperid family induces a complex pathophysiological picture characterized by spectacular changes in hemostasis and frequently hemorrhage is also seen. The present work reports the ability of six of a series of 1,2,3-triazole derivatives to inhibit some pharmacological effects caused by the venoms of Bothrops jararaca and Lachesis muta. In vitro assays showed that these compounds were impaired in a concentration-dependent manner, the fibrinogen or plasma clotting, hemolysis, and proteolysis produced by both venoms. Moreover, these compounds inhibited biological effects in vivo as well. Mice treated with these compounds were fully protected from hemorrhagic lesions caused by such venoms. But, only the B. jararaca edema-inducing activity was neutralized by the triazoles. So the inhibitory effect of triazoles derivatives against some in vitro and in vivo biological assays of snake venoms points to promising aspects that may indicate them as molecular models to improve the production of effective antivenom or to complement antivenom neutralization, especially the local pathological effects, which are partially neutralized by antivenoms.

Exploring 1,2,3-triazole derivatives by using in vitro and in silico assays to target new antifungal agents and treat Candidiasis

Candidiasis is a serious public health problem that currently affects not only immunodeficient patients with predisposing conditions, but also immunocompetent individuals. Thus, the search for new antifungal agents is required also due to the emergence of resistant strains and to the side effects of the available drugs. The aim of this study is to evaluate the in vitro antifungal profile of nine synthetic 1,2,3-triazole derivatives against four Candida species of medical importance (C. albicans, C. tropicalis, C. parapsilosis, and C. krusei), as well as to identify their in silico structure-activity relationship. Interestingly, the antifungal susceptibility tests showed the compound 5-methyl-1-(phenylamino)-1H-1,2,3-triazol-4-yl-methanol (2b) with the lowest minimal inhibitory concentration value against C. albicans strain (MIC = 8 μg/mL) similar to other promissing compounds described in the literature. According to our in silico evaluation, some stereoelectronic properties (e.g., higher values of log S and lowest unoccupied molecular orbital energy and lower number of atoms, rotatable bonds and Hydrogen bond acceptors) were correlated with the antifungal activity detected. This series reinforced the potential of 1,2,3-triazole as a promising nucleus in the search for new antifungals and may help on designing new drugs for candidiasis.

Insight into and Computational Studies of the Selective Synthesis of 6H-Dibenzo[b,h]xanthenes

Starting from 2-hydroxy-1,4-naphthoquinone (lawsone), we synthesized eight new 6H-dibenzo[b,h]xanthene derivatives selectively under solvent-free conditions. Spectroscopic investigations confirmed that only the isomer 6H-dibenzo[b,h]xanthene was obtained in all eight cases. Computational studies provide a rationalization for the selective appearance of these isomers having as an intermediate an addition product.

Synthesis and antitumor evaluation of hybrids of 5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylates and carbohydrates

AIM Cancer has emerged as a growing public health problem in many parts of the world. METHODOLOGY We describe the synthesis of a series of carbohydrate-based isoquinoline-5,8-diones through the 1,4-addition reaction between 5,8-dioxo-5,8-dihydroisoquinoline and aminocarbohydrates. Halogenated quinones were also synthesized. Their inhibitory effects on the proliferation of human cancer cell lines were studied. RESULTS & CONCLUSION The most promising compound, derived from isoquinoline-5,8-dione, containing ribofuranosidyl ring, was selectively active in vitro against H1299 cancer cells, with 1.7-fold higher activity than that of vinorelbine tartrate. This result suggests that the glycoconjugate in question may constitute a valuable lead compound to design and synthesize a more active and less toxic derivative with respect to the development of a new antitumor substance.

Efficient access to β-vinylporphyrin derivatives via palladium cross coupling of β-bromoporphyrins with N-tosylhydrazones

This work describes a new approach to obtain new β-vinylporphyrin derivatives through palladium-catalyzed cross-coupling reaction of 2-bromo-5,10,15,20-tetraphenylporphyrinatozinc(II) with N-tosylhydrazones. This is the first report of the use of such synthetic methodology in porphyrin chemistry allowing the synthesis of new derivatives, containing β-arylvinyl substituents.