Luteolin as a potent anti-leishmanial agent against intracellular Leishmania tropica parasite

Purpose: To examine the anti-leishmanial and cytotoxic effects of five naturally occurring phenolic compounds: luteolin (1), lalioside (2), luteolin-4’-O-β-D-glucopyranoside (3), apigenin 4-O-β-Dglucopyranoside (4) and apigenin (5) on Leishmania tropica KWH23 amastigotes .Methods: The compounds were isolated from the leaves of Lawsonia Inermis via hyphenated high performance liquid chromatography-high resolution mass spectrometry coupled with solid phase extraction-tube transfer nuclear magnetic resonance technique. The isolated compounds were given intraperitoneally to L. tropica KWH23 amastigotes-infected albino mice at a dose of ≥ 3 mg/kg for 5 days. Amphotericin-B was used as standard (reference) drug. Lymphocytes were used to analyze their cytotoxicity.Results: For compound 1, mean lesion size decreased from 0.82 ± 0.12 to 0.10 ± 0.01 after 120 days, with 97 % cure of intracellular L. tropica amastigotes at a dose of 15 mg/kg, compared to amphotericin B which produced 95 % cure at a dose of 30 mg/kg. Half-maximal concentration (IC50) for compound 1 was 4.15 μg/ml against lymphocytes.Conclusion: The results indicate that luteolin is a potent inhibitor of L. tropica  amastigotes, with a higher cytotoxic activity against lymphocytes, compared with luteolin-4’-O-β-D-glucopyranoside.Keywords: Leishmania tropica, Luteolin, Lalioside, Luteolin-4’-O-β-D-glucopyranoside, Apigenin 4-O- β-D-glucopyranoside, Apigeni

Synthesis of N-substituted acetamide derivatives of azinane-bearing 1,3,4-oxadiazole nucleus and screening for antibacterial activity

Purpose: To synthesize some acetamide derivatives bearing azinane and 1,3,4-oxadiazole heterocyclic cores and to evaluate their antibacterial potentials.Methods: Ethyl piperidin-4-carboxylate (2) was converted to ethyl 1-[(4-chlorophenyl)sulfonyl]piperidin- 4-carboxylate (3), 1-[(4-chlorophenyl)sulfonyl]piperidin-4-carbohydrazide (4) and 5-[1-(4-chlorophenylsulfonyl)-4-piperidinyl]-1,3,4-oxadiazol-2-thiol (5) using three consecutive steps. The target molecules, 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-{[N-(substituted)-2-acetamoyl]thio]}-1,3,4- oxadiazole (8a-n) were synthesized by stirring 5 and N-aryl-2-bromoacetamides (7a-n) in an aprotic polar solvent. The structures were corroborated by infrared (IR), electron impact mass spectrometry (EIMS) and proton/carbon nuclear magnetic resonance (1H/13C-NMR) spectroscopic techniques. The evaluation of antibacterial activity was based on the effect on the increase in absorbance of the broth medium due to log phase microbial growth.Results: Compound 8g bearing a 2-methylphenyl group was the most the active growth inhibitor of Salmonella typhi, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis bacterial strains with minimum  inhibitory concentrations (MIC) of 10.63±0.97, 10.31±1.00, 10.45 ± 0.94 and 11.77±5.00 μM, respectively. Ciprofloxacin was used as reference standard.Conclusion: All the synthesized compounds are moderate inhibitors but relatively more active against Gram-negative bacterial strains. 5-{1-[(4- Chlorophenyl)sulfonyl]piperidin-4-yl}-2-{[N-(2-methylphenyl)-2- acetamoyl]thio]}-1,3,4-oxadiazole (8g) is the most active growth inhibitor of all the strains except Staphylococcus aureus.Keywords: 1,3,4-Oxadiazole, Acetamides, Antibacterial activity, Piperidin