Raoni Schroeder Borges Gonçalves

Mefloquine–Oxazolidine Derivatives: A New Class of Anticancer Agents

A series of 23 racemic mefloquine–oxazolidine derivatives, 4‐[3‐(aryl)hexahydro[1,3]oxazolo[3,4‐a]pyridin‐1‐yl]‐2,8‐bis(trifluoromethyl)quinolines, derived from (R*, S*)‐(±)‐mefloquine and arenealdehydes, have been evaluated for their activity against four cancer cell lines (HCT‐8, OVCAR‐8, HL‐60, and SF‐295). Good cytotoxicities have been determined with IC50 values ranging from 0.59 to 4.79 μg/mL. In general compounds with aryl groups having strong electron‐releasing substituents, such as HO and MeO, or electron‐rich heteroaryl groups, for example imidazol‐2‐y‐l, are active. However, other factors such as steric effects may play a role. As both the active and non‐active conformations of the mefloquine–oxazolidine derivatives are similar, it is concluded that molecular conformations do not play a significant role either. This study is the first to evaluate mefloquine derivatives as antitumor agents. The mefloquine–oxazolidine derivatives are considered to be useful leads for the rational design of new antitumor agents.

2-Bromo­pyridine-3-carboxylic acid

The carboxylic acid residue in the title compound, C6H4BrNO2, is twisted out of the plane of the other atoms, as indicated by the (Br)C—C—C—Ocarbonyl torsion angle of −20.1 (9)°. In the crystal, supramolecular chains mediated by O—H⋯N hydrogen bonds are formed with base vector [201] and C—H⋯O interactions reinforce the packing.

In vitro anti-mycobacterial activity of (E)-N´-(monosubstituted-benzylidene) isonicotinohydrazide derivatives against isoniazid-resistant strains

A series of twenty-three N-acylhydrazones derived from isoniazid (INH 1-23) have been evaluated for their in vitro antibacterial activity against INH- susceptible strain of M. tuberculosis (RG500) and three INH-resistant clinical isolates (RG102, RG103 and RG113). In general, derivatives 4, 14, 15 and 16 (MIC=1.92, 1.96, 1.96 and 1.86 µM, respectively) showed relevant activities against RG500 strain, while the derivative 13 (MIC=0.98 µM) was more active than INH (MIC=1.14 µM). However, these derivatives were inactive against RGH102, which displays a mutation in the coding region of inhA. These results suggest that the activities of these compounds depend on the inhibition of this enzyme. However, the possibility of other mechanisms of action cannot be excluded, since compounds 2, 4, 6, 7, 12–17, 19, 21 and 23 showed good activities against katG-resistant strain RGH103, being more than 10-fold more active than INH.

Simple Methodology for the Preparation of Amino Alcohols from Amino Acid Esters Using NaBH4–Methanol in THF

Abstract Amino alcohols constitute a very useful and versatile class of organic compounds, with important applications in synthetic and medicinal chemistry. However, in most of the procedures described in the literature for the obtainment of these compounds, considerable limitations can be found, such as drastic conditions, long time reactions, poor yields, and purification problems. The present article describes a methodology that gives amino alcohols and N-protected amino alcohols based on the reduction of amino acid esters under mild conditions, employing NaBH4 in the presence of methanol. The reactions occurred in a short time (15–20 min) and provide yields of 50–95%.

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.

Lamivudine, an important drug in aids treatment

Lamivudine, an L-nucleoside, has been considered the cornerstone of antiretroviral therapy programs considering its favorable efficacy, convenient dosing, and safety profile. The low incidence of side effects in comparison with D-nucleoside analogs is due to the presence of sulfur and also to its stereochemistry difference. Considering the importance of lamivudine especially in acquired immune deficiency syndrome treatment, but also in hepatitis B infection (HBV), two critical diseases nowadays, the purpose of this article is to highlight different aspects and synthetic strategies of this important drug.

Crystal structures of three 4-[3-(XC6H4)-hexahydro[1,3] oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinolines (X = 3-MeO, 4-MeO and 4-HO)

Abstract The crystal structures of three racemic 4-{3- (X-phenyl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl}-2,8- bis (trifluoromethyl)quinolines, 2, namely (2: X = 3-MeO, 4-MeO and 4-HO), prepared from mefloquine and XC6H5CHO, are reported. All three molecules were previously reported to be active in in-vitro studies against the multidrug-resistant tuberculosis strain T113. In each of the three molecules, the piperidinyl ring has a chair shape with substituents in equatorial sites and the 1,3-oxazolidinyl ring exhibit deviations from planarity. All molecules have “F’’ shape conformations with the X-phenyl and quinoline rings lying on one side of the best plane through the fused oxazolidine-piperidine rings, and in an arrangement approaching open butterfly wings. However there are differences in the inter-planar angles. No correlation was established between the anti-TB activity and the molecular conformation. Compound (2: X = 4-MeO) has a onedimensional structure generated from C-F ... π(pyridine) and C-H ... π(methoxyphenyl) interactions. Both (2: X = 3-MeO) and (2: X = 4-HO) have three dimensional structures. The supramolecular arrangements in (2: X = 3-MeO) are derived from C-H ... O(oxazolidine), C-H ... F and C-H ... π(phenyl of quinoline) interactions and those for (2: X = 4-HO) from O-H ... N(piperidine), C-H ... O(hydroxyl), C-H ... F, C-H ... π(phenyl of quinoline), C-F ... π(pyridine), C-F ... π(imine) and p(methoxyphenyl) ... π(methoxyphenyl) interactions.

Benzyl 2-{[2,8-bis-(trifluoro-meth-yl)quinolin-4-yl](hy-droxy)meth-yl}piperidine-1-carboxyl-ate.

The title molecule, C25H22F6N2O3, adopts an open conformation whereby the quinoline and carboxylate ester groups are orientated in opposite directions but to the same side of the piperidine ring so that the molecule has an approximate U-shape. The piperidine ring adopts a distorted boat conformation. In the crystal, inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate R 2 2(14) loops.

tert-Butyl 2-{[2,8-bis-(trifluoro-meth-yl)quinolin-4-yl](hy-droxy)meth-yl}piperidine-1-carboxyl-ate.

The title molecule, C22H24F6N2O3, adopts a folded conformation whereby the carboxylate residue lies over the quinolinyl residue, with the dihedral angle between the carbamate and quinoline planes being 41.64 (7)°. Helical supramolecular C(7) chains sustained by O—H⋯O hydrogen bonds propagating along the a-axis direction feature in the crystal packing. The F atoms of one of the CF3 groups are disordered over two orientations; the major component has a site occupancy of 0.824 (7).

(R*,S*)-(±)-1-(2-{[2,8-Bis(trifluoromethyl)quinolin-4-yl](hydroxy)methyl}piperidin-1-yl)ethanone methanol monosolvate.

The title mefloquine derivative has been crystallized as its 1:1 methanol solvate, C19H18F6N2O2·CH3OH. Each of the methinehydroxyl residue [the C—C—C—O torsion angle is −16.35 (17) °] and the piperidinyl group [distorted chair conformation] lies to one side of the quinolinyl ring system. The hydroxyl and carbonyl groups lie to either side of the molecule, enabling their participation in intermolecular interactions. Thus, the hydroxyl and carbonyl groups of two centrosymmetrically related molecules are bridged by two methanol molecules via O—H⋯O hydrogen bonds, leading to a four-molecule aggregate. These are linked into a supramolecular chain along the a axis via C—H⋯O interactions involving the hydroxyl-O atom. The chains assemble into layers that interdigitate along the c axis being connected by C—H⋯F interactions.