Antimicrobial efficacy of n-[3- chloro-(substituted aryl)-4-oxoazetidin- 1-yl] pyridine-4- carboxamides against resistant bacterial strains obtained from clinical isolates

Abstract Background: The treatment of infectious diseases is still an important and challenging problem due to emerging infectious diseases and increasing number of multi-drug resistant microbial pathogens which cause a variety of illnesses ranging from hospital-acquired pneumonia, bloodstream infections, urinary tract infections from catheters, abdominal infections and even meningitis. Methods: The main objective of the present study was to evaluate the antimicrobial efficacy and β-lactamase inhibitory activity of the synthesized 2-azetidinones against resistant bacterial strains obtained from clinical isolates. Results: The tested 2-azetidinones exhibited antimicrobial efficacy comparable to the standard drugs Ampicillin and Griseofelvin. Among the tested compounds, N-[3-chloro-2-(2,5-dimethoxyphenyl)-4-oxoazetidin-1-yl]pyridine-4-carboxamide(5o) exhibited the highest activity with MIC of 6.25 µg/mL (Gram +ve and Gram –ve bacteria),1.56 µg/mL (A. niger) and 3.12 µg/mL(A. terrus and P. chrysogenum) respectively. Also all the screened compounds (5d, 5f, 5h,5j,5o) exhibited more pronounced activity (MIC: 125 µg/mL) against resistant K. pneumonia obtained from clinical isolates compared to standard antibiotic Amoxycillin. The compounds when tested as admixtures with the standard antibiotic amoxicillin (1:2) exhibited similar antibacterial spectra in comparison to the most widely employed clinical combination Augmentin. The 2-azetidinonescan prove to be a cheaper alternative with similar potential β-lactamase inhibitory activity thereby proving their utility and benefit towards the development of anti-infectives for the treatment of infections caused by drug resistant microorganisms

Synthesis and biological evaluation of Schiff’s bases and 2-azetidinones of isonocotinyl hydrazone as potential antidepressant and nootropic agents

The synthesis and pharmacological activity of N′-[(1Z)-(substituted aromatic) methylidene] pyridine-4-carbohydrazides (3a–k) and N-[3-chloro-2-(substituted aromatic)-4-oxoazetidin-1-yl]pyridine-4-carboxamides (5a–k) are described. Synthesis of 2-azetidinones was performed by novel methods of stirring and sonication involving the cyclocondensation of the appropriate Schiff’s bases (3a–k) with chloroacetyl chloride, followed by the addition of triethyl amine in the presence of molecular sieves. The compounds were investigated for their antidepressant activity, compounds N′-[(1Z)-(2,5-dimethoxyphenyl)methylidene]pyridine-4-carbohydrazide (3k) and N-[3-chloro-2-(2,5-dimethoxyphenyl)-4-oxoazetidin-1-yl]pyridine-4-carboxamide (5k) with 2,5-dimethoxy substitution on the aryl ring exhibited the highest antidepressant activity. In the elevated plus maze test and passive avoidance test in mice for the evaluation of nootropic activity N′-[(1Z)-(4-nitrophenyl)methylidene]pyridine-4-carbohydrazide (3d) and N-[3-chloro-2-(4-nitrophenyl)-4-oxoazetidin-1-yl]pyridine-4-carboxamide (5d) with para nitro substitution on the aryl ring exhibited the highest activity. All synthesised Schiff’s bases and azetidinone analogues exhibited antidepressant and nootropic activities in a dose dependant manner. The results confirmed the fact that the 2-azetidinone skeleton has potential as a CNS active agent and can be explored for the development of more potent and safe CNS active agents for therapeutic use

Evaluation of Antivenom Potential of Achyranthes Aspera Leaves Against Snake Venom

The antivenom potential of aqueous (AE) and ethanolic extract (EE) of the leaves of Achyranthes aspera plant was evaluated using in vitro assays. Soxhlet extraction of the dried, powdered leaves of Achyranthes aspera was carried out. The neutralization of lethal toxicity induced by D. russelli venom was assessed using mice. Leaf extract effectively neutralized the russeli's viper venom induced lethality (LD50) of 11 µg with effective dose (ED50) of 0.3mg for AE and 1.5mg for EE. Phospholipase A2 present in snake venom was neutralized at a dose of 0.05mg and 0.06mg of AE and EE leaf extract respectively. Further procoagulant activity was carried out using Echis carinatus venom. The extracts also effectively neutralized the venom induced hemolysis in the concentration range of 50-100µg. HPTLC analysis done for the extracts showed Rf values indicating same constituents in both extracts. The results obtained demonstrate that leaf extract of Achyranthes aspera possess snake venom neutralizing capacity and can be used as an adjuvant for antivenom therapy

A facile microwave assisted one pot synthesis of novel xanthene derivatives as potential anti-inflammatory and analgesic agents

Microwave assisted irradiation of resorcinol and substituted aryl aldehydes using sulfamic acid as catalyst afforded novel 9-aryl-9H-xanthene-3,6-diol derivatives (1a–f) in good yields. The newly synthesized compounds which were previously selected on the basis of PASS prediction were tested for anti-inflammatory activity using carrageenan-induced rat paw edema and analgesic activity using acetic acid induced writhing and formalin-induced paw edema in mice along with the estimation of gastric ulcerogenicity index. Compounds 1e and 1f exhibited significant anti-inflammatory and analgesic activities as compared to standard drug. The study also revealed that compounds (1a–f) showed minimum or no ulcerogenicity in mice as that of the standard drug