Samir A. Carvalho

5-Phenyl-2-(benzalhydrazonyl)-1,3,4-thiadiazoles, potential trypanocidal agents: consistent dimer formation via N–H · · · N intermolecular hydrogen bonds

Abstract The molecular and crystal structures of a series of 5-Ph-2-(arylCH=NNH)-1,3,4-thiadiazoles [2: aryl = 4-XC6H4 (X = H [2a], 4-Cl [2b], 4-Br [2c], 4-F3CO [2d], 2-HO [2e], 2-HO-3-MeO [2f] as well as [5-Ph-2-(4-HOC6H4CH=NNH)-1,3,4-thiadiazole]3(H2O)2] [(2g)3 · 2 (H2O)] are reported. The compounds were prepared as part of a study on typanocide reagents as possible treatments for Chagas‘ disease. The asymmetric unit of [(2g)3 · 2 (H2O)] consists of three independent molecules and two water molecules, in contrast to the single molecules comprising the asymmetric units of 2a–2f. In all cases, N–H · · · N intermolecular hydrogen bonding results in the formation of dimers linked by R22(8) rings. As well as the hydrogen-bonded dimers, the molecules of 2a–2f are also linked by other weak interactions including aromatic π–π stacking and C–H · · · X bonds.

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).

Crystal structures of 1-hydroxylimidazole and imidazole 1-oxide derivatives

Abstract The N-oxide or 1-hydroxy forms of four solid 1-hydroxy-5-(4-methyl-2-nitroimidazol-2-yl)-4-phenyl-2-(X-phenyl)-imidazole derivatives, 6, have been studied by X-ray crystallography. Compounds, (6: X=4-Br) and (6: X=2-O2N), both recrystallized from EtOH, and (6: X=4-F), recrystallized from EtOCH2CH2OH, were isolated in the 1-hydroxyimidazole form. In contrast, (6: X=H), recrystallized from EtOCH2CH2OH, was obtained in the imidazole N-oxide form. Two independent molecules, Mol A and Mol B, rotamers, are present in the asymmetric unit of the imidazole N-oxide compound, (6: X=H) and are linked into chains of alternating compounds, mainly by N–H···O hydrogen bonds, but also by N–H···N and C–H···O hydrogen bonds and π···π interactions. These chains are linked by other C–H···O and C–H···N hydrogen bonds and π···π interactions into a 3-D arrangement. In the 1-hydroxyimidazole compound, (6: X=2-O2N), classical hydrogen bonds, O1–H1···N3, are the major interactions linking molecules into C(5) chains: weak π···π stacking interactions also link the molecules within the chains. These chains are linked by C–H···O and hydrogen bonds and by N–O···π interactions into a three- dimensional array. The other 1-hydroxyimidazole compounds, (6: X=4-Br) and (6: X=4-F), have similar structures, which differ from that of (6: X=2-O2N). In (6: X=4-Br) and (6: X=4-F), pairs of classical O–H···N hydrogen bonds link molecules into symmetric dimers: these dimers are further stabilized by π···π interactions. Other intermolecular interactions found in both (6: X=4-Br) and (6: X=4-F) are C–H···O hydrogen bond and N–O···π interactions, which link the O–H···N hydrogen bonded dimers into a 3-dimensional array.

(2E)-N′-[(E)-4-Chloro­benzyl­idene]-3-phenyl­prop-2-enohydrazide monohydrate

The conformation about each of the imine and ethene bonds in the title hydrazide hydrate, C16H13ClN2O·H2O, is E. The hydrazide molecule is approximately planar (r.m.s. deviation of the 20 non-H atoms = 0.172 Å). The most significant twist occurs about the ethene bond [C—C=C—C = 164.1 (5)°] and the dihedral angle formed between the benzene rings is 5.3 (2)°]. In the crystal, the presence of N—H⋯Ow and O—H⋯Oc (× 2; w = water and c = carbonyl) hydrogen bonds leads to a supramolecular array in the bc plane.

(2E)-N'-[(E)-Benzyl-idene]-3-phenyl-prop-2-enohydrazide from synchrotron radiation.

In the title compound, C16H14N2O, the dihedral angle between the phenyl rings is 25.48 (12)°. An E conformation is found for each of the imine [1.269 (3) Å] and ethylene [1.313 (3) Å] bonds. In the crystal, molecules are linked by N—H⋯O hydrogen bonds, leading to zigzag chains along [010]. Supramolecular layers in the ab plane are formed, whereby the chains are linked by C—H⋯N and C—H⋯π interactions.

(2E)-N'-[(E)-2-Hy-droxy-benzyl-idene]-3-phenyl-prop-2-enohydrazide.

In the non-planar title compound, C16H14N2O2, the dihedral angle between the phenyl rings is 16.67 (8)°. An E conformation is found for each of the imine [1.286 (2) Å] and ethylene [1.335 (2) Å] bonds. The amide O and H atoms are anti, and an intramolecular hydroxy O—H⋯N hydrogen bond is noted. The formation of N—H⋯O(hydroxy) hydrogen bonds in the crystal packing leads to helical chains along the b axis. Supramolecular layers in the ab plane are formed as the chains are linked by C—H⋯O interactions.

5-(3-Nitro­benz­yl)-1,3,4-thia­diazol-2-amine

In the title molecule, C9H8N4O2S, the dihedral angle between the thiadiazole and benzene rings is 73.92 (8)° and the thiadiazole group S atom is orientated towards the benzene ring, the central S—C—C—C torsion angle being 45.44 (18)°. In the crystal, supramolecular tapes mediated by N—H⋯N hydrogen bonds and comprising alternating eight-membered {⋯HNCN}2 and 10-membered {⋯HNH⋯NN}2 synthons are formed along [010]. The tapes are consolidated into a three-dimensional network by a combination of C—H⋯O, C—H⋯S and C—H⋯π interactions

N'-[(2E)-3-Phenyl-prop-2-eno-yl]benzo-hydrazide.

In the title compound, C(16)H(14)N(2)O(2), the conformation about the C=C bond is E, and the two amide groups are effectively orthogonal [the C-N-N-C torsion angle is 104.5 (2)°]. In the crystal structure, the amide groups groups associate via N-H⋯O hydrogen bonding, forming supra-molecular tapes with undulating topology along the c-axis direction.

Novel Therapeutic Strategies for Chagas` Disease

Chagas’ disease, also called American trypanosomiasis, is one of the most neglected parasitic diseases in the world. An estimated 10 million people are infected worldwide, mostly in Latin America where Chagas disease is endemic. More than 25 million people are at risk of the disease. It is estimated that in 2008 Chagas disease killed more than 10,000 people. Its infectious agent is the protozoan parasite Trypanosoma cruzi with symptoms progressing from mild swelling to intestinal disease and ultimately heart failure. Currently, 2 antiparasitic drugs are recommended for the treatment of chagasic patients: nifurtimox and benznidazole. However, the effectiveness of both varies according to (i) the phase of the disease (acute and early latent infection), (ii) different parasite isolates, (iii) period of treatment and dosage and (iv) age of patient. Also, their well-known toxicity and limited effect make the search for new drugs imperative. Many trypanocidal compounds have been screened in the past few decades and some promising targets have been reported since the introduction of nifurtimox and benznidazole (1960-1970).

(2E)-N `-Benzoyl-3-(4-nitrophenyl)prop-2-enohydrazide

In the title compound, C16H13N3O4, the dihedral angle between the terminal benzene rings is 14.02 (7)°. The carbonyl groups are anti with respect to each other, which facilitates their participation in the formation of supramolecular chains. Each side of the –C(=O)N(H)N(H)C(=O)– residue associates with a centrosymmetrically related molecule, resulting in the formation of essentially flat ten-membered {⋯O=CNN(H)}2 synthons. The resultant chains are further consolidated in the crystal structure via C—H⋯O contacts.