Spiro heterocycles bearing piperidine moiety as potential scaffold for antileishmanial activity: synthesis, biological evaluation, and in silico studies.

New spiro-piperidine derivatives were synthesised via the eco-friendly ionic liquids in a one-pot fashion. The in vitro antileishmanial activity against Leishmania major promastigote and amastigote forms highlighted promising antileishmanial activity for most of the derivatives, with superior activity compared to miltefosine. The most active compounds 8a and 9a exhibited sub-micromolar range of activity, with IC50 values of 0.89 µM and 0.50 µM, respectively, compared to 8.08 µM of miltefosine. Furthermore, the antileishmanial activity reversal of these compounds via folic and folinic acids displayed comparable results to the positive control trimethoprim. This emphasises that their antileishmanial activity is through the antifolate mechanism via targeting DHFR and PTR1. The most active compounds showed superior selectivity and safety profile compared to miltefosine against VERO cells. Moreover, the docking experiments of 8a and 9a against Lm-PTR1 rationalised the observed in vitro activities. Molecular dynamics simulations confirmed a stable and high potential binding to Lm-PTR1.

Novel 2-Acetamido-2-ylidene-4-imidazole Derivatives (El-Saghier Reaction): Green Synthesis, Biological Assessment, and Molecular Docking.

El-Saghier reaction is the novel, general, and green reaction of various amines with ethyl cyanoacetate and ethyl glycinate hydrochloride. A new series of imidazolidin-4-ones and bis-N-(alkyl/aryl) imidazolidin-4-ones was synthesized in a sequential, one-pot procedure under neat conditions for 2 h at 70 °C. Excellent high yields (90-98%) were achieved in a short period of time while avoiding issues related to the hazardous solvents utilized (cost, safety, and pollution). The spectrum analyses and elemental data of the newly synthesized compounds helped us to clarify their structures. The obtained compounds were tested for antibacterial activity in vitro and compared to the standard antibiotic chloramphenicol as the standard, measuring the inhibition zone (nm) and activity index (%). With an antibacterial percentage value of 80.0 against Escherichia coli, N,N'-(propane-1,3-diyl) bis(2-(4-oxo-4,5-dihydro-1H-imidazole-2-yl) acetamide) proved to be the most effective. Antimicrobial activity was confirmed by a molecular docking investigation to investigate how chemicals bind to the bacterial FabH-CoA complex in E. coli (PDB ID: 1HNJ).

Synthesis and antimicrobial activity of some novel 1,2-dihydro-[1,2,4]triazolo[1,5-a]pyrimidines bearing amino acid moiety.

A new series of [1,2,4]-triazole bearing amino acid derivatives 2a-d-9a-d were synthesized under green chemistry conditions via multicomponent reaction using lemon juice as an acidic catalyst. The obtained compounds were characterized by different spectral and elemental analyses. The obtained candidates showed promising antibacterial activity against some standard bacteria and multidrug resistant (MDR) clinical isolates. In contrast to the reference drugs cephalothin and chloramphenicol, the tested compounds showed substantial better MIC values towards the tested MDR strains. The most active compounds 3c, 8a and 9d against MDR bacteria were tested for MBC and MIC index, the results indicted the bacteriostatic activity of these compounds. The most active compounds 2c, 2d, 3c, 8a, 8b, 9a, 9b, 9c and 9d showed a high selectivity index towards antimicrobial activity against K. pneumoniae and MRSA1 compared to mammalian cells, suggesting a good safety profile.