Thais C. M. Nogueira

Design, synthesis and biological evaluation of (E)-2-(2-arylhydrazinyl)quinoxalines, a promising and potent new class of anticancer agents

A series of forty-seven quinoxaline derivatives, 2-(XYZC6H2CHN-NH)-quinoxalines, 1, have been synthesized and evaluated for their activity against four cancer cell lines: potent cytotoxicities were found (IC50 ranging from 0.316 to 15.749 μM). The structure-activity relationship (SAR) analysis indicated that the number, the positions and the type of substituents attached to the aromatic ring are critical for biological activity. The activities do not depend on the electronic effects of the substituents nor on the lypophilicities of the molecules. A common feature of active compounds is an ortho-hydroxy group in the phenyl ring. A potential role of these ortho-hydroxy derivatives is as N,N,O-tridentate ligands complexing with a vital metal, such as iron, and thereby preventing proliferation of cells. The most active compound was (1: X,Y=2,3-(OH)2, Z=H), which displayed a potent cytotoxicity comparable to that of the reference drug doxorubicin.

N-(4-Bromo­phen­yl)-2-(2-thien­yl)acetamide

The thienyl ring in the title compound, C12H10BrNOS, is disordered over two diagonally opposite positions, the major component having a site-occupancy factor of 0.660 (5). The molecule is twisted as evidenced by the dihedral angles of 70.0 (4) and 70.5 (6)° formed between the benzene ring and the two orientations of the disordered thiophene ring. Linear supramolecular chains along the a axis are found in the crystal structure through the agency of N—H⋯O hydrogen bonding.

Synthesis and antitubercular activity of new L-serinyl hydrazone derivatives.

A series of 32 L-serinyl hydrazone derivatives have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv, being also evaluated their cell viabilities in non infected and infected macrophages with Mycobacterium bovis Bacillus Calmette-Guerin (BCG). The compounds 8c, 8e, 8h and 8i, were non-cytotoxic and exhibited an important minimum inhibitory concentration (MIC) activity between 25 and 100 μg/mL, which can be compared with that of the tuberculostatic drug D-cicloserine (5-20 μg/mL).

Synthesis and Biological Evaluation of N,N′-di(thiopheneacetyl)diamines Series as Antitubercular Agents

The series of new N,N′-di(thiopheneacetyl)diamines derivatives, 8–17, were synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis(TB), and the activity expressed as the minimum inhibitory concentration (MIC) in μ g/mL. Compound 13 was the only one determined to be active and exhibited a MIC 50 μg/mL, indicating that the alkyl chain-length of the diamines is critical for biological activity. This class of compound has not been evaluated before, and it could be a good starting point to find new lead compounds in the fight against multi-drug resistant TB.

N -acylhydrazones containing thiophene nucleus: a new anticancer class

In this study, we present a series of N-acylhydrazones containing thiophene nuclei as a new anticancer class. Fifty-seven compounds in this series were evaluated for their activity against four human cancer cell lines. Cytotoxicity (IC50) ranged from 0.82 to 12.90 μM. The compound (E)-N′-(2-hydroxy-3-methoxybenzylidene)thiophene-2-carbohydrazide displayed good cytotoxic activity in all cell lines (IC50 = 0.82–5.36 μM) and yielded the best result in this series; therefore, it is an important lead compound in this new class.

Quinoxaline Nucleus: A Promising Scaffold in Anti-cancer Drug Discovery

Heterocyclic compounds are a class of substances, which play a critical role in modern drug discovery being incorporated in the structure of a large variety of drugs used in many different types of diseases. Quinoxaline is an important heterocyclic nucleus with a wide spectrum of biological activities, and recently much attention has been found on anticancer drug discovery based on this class. Owing to the importance of this system, the aim of this review is to provide an update on the synthesis and anticancer activity of quinoxaline derivatives covering articles published between 2010 and 2015.

N'-[(1E)-(5-Nitro-furan-2-yl)methyl-idene]thio-phene-2-carbohydrazide: crystal structure and Hirshfeld surface analysis.

The title molecule is curved as seen in the dihedral angle [27.4 (2)°] between the outer rings. Supramolecular chains about a 41 screw axis are formed by amide-N—H⋯O(carbonyl) hydrogen bonding.

Design, Synthesis and Anti-tuberculosis Activity of Hydrazones and N-acylhydrazones Containing Vitamin B6 and Different Heteroaromatic Nucleus

Background: The term vitamin B6 refers to a set of six compounds, pyridoxine, pyridoxal ,and pyridoxamine and their phosphorylated forms, among which pyridoxal 5´-phosphate (PLP) is the most important and active form acting as a critical cofactor. These compounds are very useful in medicinal chemistry because of their structure and functionalities and are also used in bioinorganic chemistry as ligands for complexation with metals. Methods: In this study, a series of hydrazones 1a-g and N-acylhydrazones 2a-f containing vitamin B6 have been synthesized from commercial pyridoxal hydrochloride and the appropriate aromatic or heteroaromatic hydrazine or N-acylhydrazine. All synthesized compounds have been fully characterized and tested against Mycobacterium tuberculosis. Results: Among the N-acylhydrazones derivatives 2a-f, 2d (para- pyridine substituted Nacylhydrazone; MIC = 10.90 μM) exhibited the best activity. The ortho-pyridine derivative 2b exhibited intermediate activity (MIC = 87.32 μM), and the meta-pyridine derivative 2c was inactive. In case of the hydrazone series 1a-g, 7-chloroquinoxaline derivative 1f (MIC = 72.72 μM) showed the best result, indicating that the number of nitrogen and chlorine atoms in the radical moiety play an important role in the anti-tuberculosis activity of the quinoxaline derivatives (1f and 1g). Conclusion: The data reported herein indicates that the isoniazid derivative 2d (MIC = 10.90 μM) exhibited the best activity in the N-acylhydrazone series and; the quinoxaline nucleus derivative 1f (MIC = 72.72 μM) was the most active compound in the hydrazone series.

Synthesis, Biological Activity, and Mechanism of Action of 2-Pyrazyl and Pyridylhydrazone Derivatives, New Classes of Antileishmanial Agents

In this work, we report the antileishmanial activity of 23 compounds based on 2‐pyrazyl and 2‐pyridylhydrazone derivatives. The compounds were tested against the promastigotes of Leishmania amazonensis and L. braziliensis, murine macrophages, and intracellular L. amazonensis amastigotes. The most potent antileishmanial compound was selected for investigation into its mechanism of action. Among the evaluated compounds, five derivatives [(E)‐3‐((2‐(pyridin‐2‐yl)hydrazono)methyl)benzene‐1,2‐diol (2 b), (E)‐4‐((2‐(pyridin‐2‐yl)hydrazono)methyl)benzene‐1,3‐diol (2 c), (E)‐4‐nitro‐2‐((2‐(pyrazin‐2‐yl)hydrazono)methyl)phenol (2 s), (E)‐2‐(2‐(pyridin‐2‐ylmethylene)hydrazinyl)pyrazine (2 u), and (E)‐2‐(2‐((5‐nitrofuran‐2‐yl)methylene)hydrazinyl)pyrazine (2 v)] exhibited significant activity against L. amazonensis amastigote forms, with IC50 values below 20 μm. The majority of the compounds did not show any toxic effect on murine macrophages. Preliminary studies on the mode of action of members of this hydrazine‐derived series indicate that the accumulation of reactive oxygen species (ROS) and disruption of parasite mitochondrial function are important for the pharmacological effect on L. amazonensis promastigotes.