Jadwiga Kaleta

3-Acylamino-azetidin-2-one as a novel class of cysteine proteases inhibitors

A new class of inhibitors for cysteine proteases cathepsin B, L, K and S is described. These inhibitors are based on the beta-lactam ring designed to interact with the nucleophilic thiol of the cysteine in the active site of cysteine proteases. Some 3-acylamino-azetidin-2-one derivatives showed very potent inhibition activities for cathepsins L, K and S at the nanomolar or subnanomolar IC(50) values.

6-Acylamino-penam derivatives: synthesis and inhibition of cathepsins B, L, K, and S.

The synthesis of a new series of 6-acylamino penam derivatives and their inhibition of cysteine proteases cathepsins B, L, K, and S is described. The 6-acylamino-penam sulfone compounds showed excellent cathepsin L, K, and S inhibition activity with IC(50) values in the nanomolar and subnanomolar range.

Synthesis of 7α-methoxy-2-(1,3-dithiolan-2-ylidene)cephem sulphones. A new series of human leukocyte elastase inhibitors

Abstract Treatment of 3-methyl-3-cephem sulphone with sodium hydride followed by carbon disulphide and alkyl halide provides an entry to 2-(1,3-diothiolan-2-ylidene)-cephem derivatives, which are new potent inhibitors of HSE.

Design and synthesis of 6-substituted amino-4-oxa-1-azabicyclo[3,2,0]heptan-7-one derivatives as cysteine proteases inhibitors.

A series of 6-substituted amino-4-oxa-1-azabicyclo[3,2,0]heptan-7-one compounds was designed and synthesized as a new class of inhibitors for cysteine proteases cathepsins B, L, K, and S. One compound (5S,6S)-6-(N-benzyloxycarbonyl-L-phenylalanyl) amino-4-oxa-1-azabicyclo[3,2,0]heptan-7-one showed excellent cathepsin L and K inhibition activity with IC(50) at a low nanomolar range.

7α-methoxy-2-[(substituted)methylene]cephem sulfones as inhibitors of human leukocyte elastase and thrombin

A series of 7α-methoxy-2-[(substituted)methylene]cephem sulfones was synthesized. The compounds with an acetoxy group at the C-3′ position as a leaving group were found to be potent inhibitors of HLE. Selected compounds are also found to be antithrombin agents.

Leupeptazin, a highly modified tripeptide isolated from cultures of a Streptomyces sp. inhibits cathepsin K

Using a human cathepsin K-targeting inhibitor screen, a new leupeptin analogue, leupeptazin (1), containing an unprecedented piperidinotriazine moiety, was isolated from a liquid culture of soil Streptomyces sp. IS2-4 collected in northern Italy. The structure of leupeptazin was established using HRESIMS as well as 1D and 2D NMR data. The inhibitory activity of the compound towards the collagenase cathepsin K was tested in vitro to reveal moderate activity with an inhibition constant, Ki, of 44μM.

Synthesis and human leukocyte elastase inhibitory activity of novel 2-spiro(2′,2′-diphenylcyclopropane) cephalosporin sulfones

A new series of 2-spiro(2′,2′-diphenylcyclopropane) cephalosporin sulfones was synthesizes as potent human leukocyte elastase inhibitors.