Siham Lahsasni

Synthesis, antimicrobial, and anti-inflammatory activity, of novel S -substituted and N -substituted 5-(1-adamantyl)-1,2,4-triazole-3-thiols

The reaction of 5-(1-adamantyl)-4-phenyl-1,2,4-triazoline-3-thione (compound 5) with formaldehyde and 1-substituted piperazines yielded the corresponding N-Mannich bases 6a–f. The reaction of 5-(1-adamantyl)-4-methyl-1,2,4-triazoline-3-thione 8 with various 2-aminoethyl chloride yielded separable mixtures of the S-(2-aminoethyl) 9a–d and the N-(2-aminoethyl) 10a–d derivatives. The reaction of compound 5 with 1-bromo-2-methoxyethane, various aryl methyl halides, and ethyl bromoacetate solely yielded the S-substituted products 11, 12a–d, and 13. The new compounds were tested for activity against a panel of Gram-positive and Gram-negative bacteria and the pathogenic fungus Candida albicans. Compounds 6b, 6c, 6d, 6e, 6f, 10b, 10c, 10d, 12c, 12d, 12e, 13, and 14 displayed potent antibacterial activity. Meanwhile, compounds 13 and 14 produced good dose-dependent anti-inflammatory activity against carrageenan-induced paw edema in rats.

POM analyses of Raltegravir derivatives: a new reflection enlightening the mechanism of HIV-integrase inhibition

Petra/Osiris/Molinspiration analysis (POM) is a promising new bioinformatical approach to establish structure and activity correlations. In the present study, we have reported the POM analyses of Raltegravir analogues that have aimed to figure out the structural features of HIV-integrase inhibitory activity. The resulting model exhibited two controllable bidentate O, O-pockets taken into consideration contributions from the steric and electrostatic fields. The POM analysis has provided interesting insights into the understanding the steric and electronic structural requirements for HIV-IN inhibitory activity. Furthermore, all the molecules were subjected to the toxicity assessment using Molinspiration and Osiris calculations. Among the various HIV-IN inhibitors, compound 27 (Raltegravir) displayed optimum drug-like characteristic activity with low toxicity. The mechanism of HIV-integrase inhibition by different Raltegravir derivatives is also discussed. This study also concluded that the bioactivity of DKA analogues should be discussed on the basis of catalytic activity of bimetallic complexes, not just on the basis of DKA or Raltegravir/HIV-integrase interaction.

Impact of Geometric Parameters, Charge, and Lipophilicity on Bioactivity of Armed Quinoxaline, Benzothiaole, and Benzothiazine: Pom Analyses of Antibacterial and Antifungal Activity

Abstract A series of four different armed heterocyclic candidates; 1-(2-methyl-2,3-dihydro-1,3-benzothiazol-2-yl)acetone (2), 1-(3-methyl-4H-1,4-benzothiazin-2-yl)ethanone (3), 2-[(2-aminophenyl)dithio]aniline (4), and 3-hydroxy-3-methyl-4-(3-methyl-2-quinoxalinyl)-2-butanone (5) have been prepared and their microbial activities were evaluated. A correlation of the structure and activities relationships of these compounds with respect to molecular modeling, Lipinski Rule of Five, drug likeness, toxicity profiles, and other physico-chemical properties of drugs are described and verified experimentally. GRAPHICAL ABSTRACT

2-{[5-(Adamantan-1-yl)-4-methyl-4H-1,2,4-triazol-3-yl]sulfan-yl}-N,N-dimethyl-ethanamine.

In the title compound, C17H28N4S, the 1,2,4-triazole ring is nearly planar [maximum deviation = 0.005 (2) Å]. There are no significant hydrogen bonds observed in the crystal structure. The crystal studied was a non-merohedral twin, the refined ratio of twin components being 0.281 (3):0.719 (3).

Microwave-And Ultrasound-Assisted Synthesis of Some Acyclonucleobases Based on a Uracil Moiety Using Dmap as Base

In this study, 1-(bromoalkanoyl)-1H-pyrimidine-2,4-diones, (2,4-dioxo-pyrimidin-1-yl)-oxo-alkanoic acids, and bis(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-alkanones were successfully prepared via electrophilic substitution of uracil and its derivatives. High yields and pure products were obtained when microwave and ultrasound methodologies were used for undertaking the reactions. Importantly, the use of 4-dimethylaminopyridine in the present investigation gave rise to higher conversions of the starting material and afforded facile access to regioselective N-1 products.

3-(1-Adamant-yl)-4-amino-1-(2-benzoyl-1-phenyl-eth-yl)-1H-1,2,4-triazol-5(4H)-thione.

In the title compound, C27H30N4OS, the 3-(adamantan-1-yl)-4-amino-1H-1,2,4-triazole-5(4H)-thione unit and the O atom are each disordered over two sets of sites with refined site-occupancies of 0.7630 (13) and 0.2370 (13). The 1,2,4-triazole ring of the major component forms dihedral angles of 62.61 (17) and 61.93 (16)° with the benzene rings, while that of the minor component makes corresponding angles of 86.3 (4) and 79.1 (4)°. The dihedral angle between the benzene rings is 39.21 (16)°. The molecular structure is stabilized by an intramolecular C—H⋯N hydrogen bond, which generates an S(6) ring motif. In the crystal, molecules are linked into inversion dimers by pairs of N—H⋯S hydrogen bonds.

N'-[(1E)-(4-Fluoro-phen-yl)methyl-idene]thio-phene-2-carbohydrazide.

In the title compound, C12H9FN2OS, the thienyl ring is disordered over two positions, with the S atom of the major component [occupancy = 87.08 (16)°] oriented towards the ortho-H atom of the benzene ring. The molecule is nearly planar, the dihedral angle between the thiophene and benzene rings being 13.0 (2)° in the major component. The azomethine C=N double bond in the molecule is of an E configuration. In the crystal, molecules are linked by pairs of N—H⋯O hydrogen bonds, forming inversion dimers.

Antimicrobial/antioxidant activity and POM analyses of novel 7-o-β-d-glucopyranosyloxy-3-(4,5-disubstituted imidazol-2-yl)-4H-chromen-4-ones

A series of 7-o-β-d-glucopyranosyloxy-3-(4,5-disubstituted imidazol-2-yl)-4H-chromen-4-ones 4 were synthesized and tested for in vitro antibacterial/antifungal and antioxidant activity. The synthesized compounds o-β-d-glucoside of 7-hydroxyl-3-imidazolyl-4H-chromen-4-ones showed good antibacterial/antifungal activity as well as antioxidant activity. The results suggest that aglycone as well as their o-glucosides could be promising candidates for new combined antifungal/antibacterial as well as antioxidant agents (3 in 1). Experimental data and Petra/Osiris/Molinspiration (POM) analyses, respectively, show high bioactivity against various microorganisms at a very low concentration without any side effect, suggesting that series 2–4 is a potential antimicrobial inhibitor and further it deserves to be validated for in vivo studies.Graphical Abstract7-Hydroxy-3-(4,5-disubstituted imidazol-2-yl)-4H-chromen-4-ones and their o-β-d-glucosides were synthesized and evaluated for in vitro antimicrobial and antioxidant activity. The compounds were also subjected to high-throughput POM bioinformatics to study the bioavailability.

Synthesis of Novel 1-(3′-CHLORO-1′,4′-DIOXO-1′,4′-Dihydronaphthalen-2′-YL)-5-Substitued-1H-Pyrimidine-2,4-Dione as Potential Antibacterial Agents

A series of new pyrimidine analogs carrying 1,4-naphthoquinone and uracil moiety were prepared as hybrid compounds 1-(3′-chloro-1′,4′-dioxo-1′,4′-dihydronaphthalen-2′-yl)-5-substitued-1H-pyrimidine-2,4-diones (6 – 9), which might possess biological activity. The structures of new products were confirmed by IR, 1H and 13C NMR, and mass spectroscopy data. All synthesized compounds were also evaluated for their antibacterial activity. The structure – activity relationship for these compounds was studied and the results showed that 1-(3′-chloro-1′,4′-dioxo-1′,4′-dihydronaphthalen-2′-yl)-5-fluoro-1H-pyrimidine-2,4-dione (9) containing a fluorine atom exhibited in vitro potent antibacterial activity (MIC50 = 1.0 μg/mL) comparable with that of the clinically useful antibacterial drug gentamicin (MIC50 = 2.0 μg/mL) against S. aureus and B. subtilis. Compound 9 also exhibited the same antibacterial activity with MIC50 = 1.0 mg/mL compared to gentamicin and ciprofloxacin against P. aeruginosa and with MIC50 = 0.5 mg/mL compared to Gentamicin (MIC50 = 0.5 mg/mL) against E. coli.

Synthesis, Characterization, and Antibacterial and Anti-Inflammatory Activities of New Pyrimidine and Thiophene Derivatives

Substituted[4,5]thieno[2,3-d]thiazolo[3,2-a]pyrimidin-5-one (3a–b) and pyrimidin-5(6H)-imine (3c–e) were synthesized via reaction of the starting compounds, ethyl 2-amino-substituted[b]thiophene-3-carboxylate (2a–c) and 2-amino-substituted [b]thiophene-3-carbonitrile (2d–f), respectively, with 2-bromothiazole. Synthesis of (bromo-substituted[b]thiophen-2-yl)alkanamide derivatives (4a–e) and thieno[2,3-d][1,3]oxazin-4-imine derivative (5) was accomplished via reaction of the starting compounds with bromoalkyl chloride through nucleophilic substitution; however, for the synthesis of compound 5, nucleophilic substitution was followed by nucleophilic addition to a nitrile group to form the oxazinimine ring. 1-(3-cyano-substituted[b]thiophen-2-yl)-3-(4-(trifluoromethyl)phenyl)thiourea derivatives (6a–c) were obtained via reaction of the starting compounds (2d–f) and 4-(trifluoromethyl phenyl)isothiocyanate. The lead compounds (2d–f) rapidly reacted with 4-(trifluoromethyl)benzaldehyde or 4-(2-pyridyl)benzaldehyde in acidic medium to yield compounds (7a–f) in large quantities. X-ray crystallography of compounds 4c and 7e confirmed their structures. Antimicrobial studies revealed that compound 6a was equally potent to ampicillin against Bacillus strains. Moreover, compounds 3e, 4d, and 6a possessed greater anti-inflammatory potency than that of the standard drug.