Ten new thiosemicarbazone derivatives, furan-2-carbaldehyde thiosemicarbazone (1), 3-methyl-furan-2-carbaldehyde thiosemicarbazone (2), 5-hydroxymethyl-furan-2-carbaldehyde thiosemicarbazone (3), 5-trifluoromethyl-furan-2-carbaldehyde thiosemicarbazone (4), 5-nitro-furan-2-carbaldehyde thiosemicarbazone (5), 5-phenyl-furan-2-carbaldehyde thiosemicarbazone (6), 5-(2-fluorophenyl)-furan-2-carbaldehyde thiosemicarbazone (7), 5-(4-methoxyphenyl)-furan-2-carbaldehyde thiosemicarbazone (8), 5-(1-naphthyl)-furan-2-carbaldehyde thiosemicarbazone (9), and 5-(1H-Pyrazol-5-yl)-furan-2-carbaldehyde thiosemicarbazone (10) were synthesized by condensing thiosemicarbazide with the respective furan-2-carbaldehyde in methanol. The prepared compounds were characterized by spectroscopic studies (FT-IR and NMR) and electrospray mass spectrometry. The molecular structures of 2, 6, 7, and 8 have also been determined by X-ray crystallography. Compounds 2, 6, and 7 crystallize in the E conformation about the N1-C6, N1-C11, and N1-C11 bonds, respectively, while 8 adopts the Z conformation about the N1-C12 bond with the presence of an intramolecular N2-HO2 hydrogen bond. All prepared thiosemicarbazone derivatives were evaluated for their in vitro antibacterial, antifungal, and antitumor activities against Staphylococcus aureus strains, Candida albicans/Candida tropicalis fungi, and seven human tumor cell lines (HuTu80, H460, DU145, M-14, HT-29, MCF-7, and LNCaP), respectively. The antioxidant activity was also studied by the DPPH assay. Compound 5 exhibited significant antibacterial activity against Staphylococcus aureus ATCC700699 (MIC=1μg/mL) compared to the nitrofurantoin and gentamicin reference drugs (MIC=125 and 10->100μg/mL, respectively). Compound 4 was ten times less active than amphotericin B (MIC=5μg/mL) against Candida albicans (ATCC90028 and ATCC10231), while 1 exhibited a moderate effect of scavenging of DPPH radical (IC₅₀=40.9μg/mL) in comparison to ascorbic acid reference compound (IC₅₀=22.0μg/mL). Among all the studied thiosemicarbazones, 5 showed a higher cytotoxic activity (IC₅₀=13.3627.73μ) in relation to the other tested compounds (IC₅₀=34.84>372.34μ) against all tested cell lines, except the LNCaP cell line, exhibiting its highest antiproliferative activity (IC₅₀=13.36μ) on the HuTu80cell line. Besides, 8 and 9 exhibited high antitumor activity (IC₅₀=13.31 and 7.69μ, respectively) against the LNCaP cells.

Four indole-3-carbaldehyde semicarbazone derivatives, 2-((5-bromo-1H-indol-3-yl)methylene)hydrazinecarboxamide (1), 2-((5-chloro-1H-indol-3-yl)methylene)hydrazinecarboxamide (2), 2-((5-methoxy-1H-indol-3-yl)methylene)hydrazinecarboxamide (3), and 2-((4-nitro-1H-indol-3-yl)methylene)hydrazinecarboxamide (4) were synthesized and characterized by ESI-MS and spectroscopic (FT-IR, ¹H NMR, and ¹³C NMR) techniques. The two-dimensional NMR (in acetone-d₆) spectral data revealed that the molecules 1 and 2 in solution are in the cisE isomeric form. This evidence is supported by DFT calculations at the B3LYP/6-311++G(d,p) level of theory where it was shown that the corresponding most stable conformers of the synthesized compounds have a cisE geometrical configuration, in both the gas and liquid (acetone and DMSO) phases. The in vitro antibacterial activity of compounds 1–4 was determined against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria. Among all the tested semicarbazones, 1 and 2 exhibited similar inhibitory activities against Staphylococcus aureus (MIC = 100 and 150 μg/mL, respectively) and Bacillus subtilis (MIC = 100 and 150 μg/mL, respectively). On the other hand, 3 and 4 were relatively less active against the tested bacterial strains compared with 1, 2, and tetracycline.

Eight new thiosemicarbazone derivatives, 6-(1-trifluoroethoxy)pyridine-3-carbaldehyde thiosemicarbazone (1), 6-(4′-fluorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (2), 5-chloro-pyridine-3-carbaldehyde thiosemicarbazone (3), 2-chloro-5-bromo-pyridine-3-carbaldehyde thiosemicarbazone (4), 6-(3′,4′-dimethoxyphenyl)pyridine-3-carbaldehyde thiosemicarbazone (5), 2-chloro-5-fluor-pyridine-3-carbaldehyde thiosemicarbazone, (6), 5-iodo-pyridine-3-carbaldehyde thiosemicarbazone (7), and 6-(3′,5′-dichlorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (8) were synthesized, from the reaction of the corresponding pyridine-3-carbaldehyde with thiosemicarbazide. The synthesized compounds were characterized by ESI-Mass, UV-Vis, IR, and NMR (¹H, ¹³C, ¹⁹F) spectroscopic techniques. Molar mass values and spectroscopic data are consistent with the proposed structural formulas. The molecular structure of 7 has been also confirmed by single crystal X-ray diffraction. In the solid state 7 exists in the E conformation about the N2-N3 bond; 7 also presents the E conformation in solution, as evidenced by ¹H NMR spectroscopy. The in vitro antitumor activity of the synthesized compounds was studied on six human tumor cell lines: H460 (lung large cell carcinoma), HuTu80 (duodenum adenocarcinoma), DU145 (prostate carcinoma), MCF-7 (breast adenocarcinoma), M-14 (amelanotic melanoma), and HT-29 (colon adenocarcinoma). Furthermore, toxicity studies in 3T3 normal cells were carried out for the prepared compounds. The results were expressed as IC₅₀ and the selectivity index (SI) was calculated. Biological studies revealed that 1 (IC₅₀ = 3.36 to 21.35 μM) displayed the highest antiproliferative activity, as compared to the other tested thiosemicarbazones (IC₅₀ = 40.00 to >582.26 μM) against different types of human tumor cell lines. 1 was found to be about twice as cytotoxic (SI = 1.82) than 5-fluorouracile (5-FU) against the M14 cell line, indicating its efficiency in inhibiting the cell growth even at low concentrations. A slightly less efficient activity was shown by 1 towards the HuTu80 and MCF7 tumor cell lines, as compared to that of 5-FU. Therefore, 1 can be considered as a promising candidate to be used as a pharmacological agent, since it presents significant activity and was found to be more innocuous than the 5-FU anticancer drug against the 3T3 mouse embryo fibroblast cells.

Eight new phenylisoxazole isoniazid derivatives, 3-(2-fluorophenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (1), 3-(2-methoxyphenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (2), 3-(2-chlorophenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (3), 3-(3-clorophenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (4), 3-(4-bromophenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (5), 5-(4-methoxiphenyl)isoxazole-3-carbaldehyde isonicotinylhydrazone (6), 5-(4-methylphenyl)isoxazole-3-carbaldehyde isonicotinylhydrazone (7), and 5-(4-clorophenyl)isoxazole-3-carbaldehyde isonicotinylhydrazone (8), have been synthesized and characterized by FT-IR, ¹H-NMR, ¹³C-NMR, and mass spectral data. The 2D NMR (¹H-¹H NOESY) analysis of 1 and 2 confirmed that these compounds in acetone-d₆ are in the trans(E) isomeric form. This evidence is supported by computational calculations which were performed for compounds 18, using DFT/B3LYP level with the 6-311++G(d,p) basis set. The in vitro antituberculous activity of all the synthesized compounds was determined against the Mycobacterium tuberculosis standard strains: sensitive H37Rv (ATCC-27294) and resistant TB DM97. All the compounds exhibited moderate bioactivity (MIC=0.340.41μM) with respect to the isoniazid drug (MIC=0.91μM) against the H37Rv sensitive strain. Compounds 6 (X=4-OCH₃) and 7 (X=4-CH₃) with MIC values of 12.41 and 13.06μM, respectively, were about two times more cytotoxic, compared with isoniazid, against the resistant strain TB DM97.

Seven species of lichens such us Umbilicaria aff. calvescens, Hypotrachyna enderythraea, Punctelia graminicola, Cladonia chlorophaea, Xanthoparmelia farinose, Psiloparmelia distincta (rock and tree substrates; rs and ts), and Usnea durietzii were collected from the province of Arequipa - Peru. Their usnic acid (UA) and fatty acid (FA) amounts in methanol-acetone were determined by High-performance liquid chromatography with diode-array detection (HPLC-DAD) and Gas chromatography-flame ionization detector (GC-FID). The antimicrobial activities of these extracts were evaluated against Staphylococcus aureus ATCC strains (43300, 29213, 25923 and 700699), Escherichia coli strains (O157:H7 and ATCC 10536), Salmonella enterica sv typhimurium ATCC 14028, Candida albicans ATCC 90028 and Candida. tropicalis ATCC 750T. In addition, antioxidant capacity was also studied by Total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical, 2,2-Azino-bis-3-ethylbenzothiazoline-6-sulfonic Acid (ABTS) radical cation and Ferric Reducing Antioxidant Power (FRAP) assays. The UA contents in all the studied lichen species varied between 0.017 and 0.304 %. Among all the tested extracts, Usnea durietzii had the highest total FA concentration (5.81 mg/g). P. distincta (rs) was active against S. aureus strains (MIC = 0.02–0.2 mg/mL) as well as C. albicans (MIC = 4 mg/mL) and C. tropicalis (MIC = 3 mg/mL). P. distincta (ts) displayed moderate total phenol content (TPC = 29.1 ± 1.6 mg GAE/g) and antioxidant capacity evidenced by scavenging DPPH (IC₅₀ = 1.45 ± 0.03 mg/mL) and ABTS (18.2 ± 0.2 mg TE/g) radicals, but it showed high values of FRAP (1953 ± 87 μM Fe²⁺/g). Our findings indicate that P. distincta (rs) could be considered as a potential antimicrobial metabolites source whereas P. distincta (ts) and Puntelia graminicole for polyphenols with antioxidant compound.

Six novel phenylisoxazole semicarbazone derivatives 1–6 were synthesized by reaction of the corresponding phenylisoxazole‐3/5‐carbaldehyde derivatives with semicarbazide hydrochloride. The synthesized compounds were characterized by ESI‐MS, FT‐IR, and NMR (¹H, ¹³C) spectroscopic techniques. The two‐dimensional ¹H‐¹H NOESY NMR (in acetone‐d₆) data revealed that compound 1 exists in the E isomeric form. The computational study of the energetic, structural, and electronic properties, carried out at B3LYP/6‐311G++(d,p) level of theory, showed that the most stable conformer for the all synthesized compounds, in both gas and liquid (acetone and DMSO) phases, has a cisE geometrical configuration. This evidence found is in good agreement with the spectrometric results. The geometrical parameters, frontier molecular orbital (FMO), molecular electrostatic potential (MEP), Mulliken atomic charges, and natural bonding orbital (NBO) analysis were also performed at the same level of theory. Taking into account the relative enthalpies ΔH computed, we can establish for tautomeric structures of each of the compounds, the following stability order: I (cisE) > II (E′E) > III (cisE). The MEP descriptors indicate that the oxygen atom of the carbonyl group C=O is susceptible to electrophilic attack, while the hydrogen atoms of the amide and hydrazone fragments are sensitive to nucleophilic attack. The calculated HOMO‐LUMO gap energies E_g indicate that 5 (in gas phase) and 6 (in liquid phase) are the most stable and less reactive compounds, while 1 is the less stable and the most reactive compound. From the NBO analysis, it becomes evident that the presence of the hydrazone fragment produces stabilizing effects due to hyperconjugative interactions.