1220850-03-2Relevant academic research and scientific papers
Broad spectrum anti-infective properties of benzisothiazolones and the parallels in their anti-bacterial and anti-fungal effects
Gopinath,Yadav,Shukla,Srivastava,Puri,Muraleedharan
, p. 1291 - 1295 (2017)
Various mono- and bis-benzisothiazolone derivatives were synthesized and screened against different strains of bacteria and fungi in order to understand the effect of multiple electrophilic sulfur atoms and substitution pattern in the immediate vicinity of reactive sulfur. Staphyllococcus aureus-ATCC 7000699, MRSA and S. aureus-ATCC 29213 (Quality Control strain) were more susceptible to this class of compounds, and the most potent derivative 1.15 had MIC50 of 0.4?μg/mL (cf. Gentamicin?=?0.78?μg/mL). CLogP value, optimally in the range of 2.5–3.5, appeared to contribute more to the activity than the steric and electronic effects of groups attached at nitrogen. By and large, their anti-fungal activities also followed a similar trend with respect to the structure and CLogP values. The best potency of IC50?=?0.1?μg/mL was shown by N-benzyl derivative (1.7) against Aspergillus fumigatus; it was also potent against Candida albicans, Cryptococcus neoformans, Sporothrix schenckii, and Candida parapsilosis with IC50 values ranging from 0.4 to 1.3?μg/mL. Preliminary studies also showed that this class of compounds have the ability to target malaria parasite with IC50 values in low micromolar range, and improvement of selectivity is possible through structure optimization.
An efficient copper mediated synthetic methodology for benzo[d]isothiazol- 3(2H)-ones and related sulfur-nitrogen heterocycles
Bhakuni, Bhagat Singh,Balkrishna, Shah Jaimin,Kumar, Amit,Kumar, Sangit
supporting information; experimental part, p. 1354 - 1357 (2012/04/10)
A copper mediated sulfur-nitrogen coupling reaction for the synthesis of benzo[d]isothiazol-3(2H)-ones and related sulfur-nitrogen heterocycles has been presented, which requires 2-halo-arylamides, sulfur powder, 25-50 mol % of copper iodide/1,10-phenanthroline, and potassium carbonate as base.
Exploring the structural requirements for inhibition of the ubiquitin E3 ligase breast cancer associated protein 2 (BCA2) as a treatment for breast cancer
Brahemi, Ghali,Kona, Fathima R.,Fiasella, Annalisa,Buac, Daniela,Soukupová, Jitka,Brancale, Andrea,Burger, Angelika M.,Westwell, Andrew D.
supporting information; experimental part, p. 2757 - 2765 (2010/08/20)
The zinc-ejecting aldehyde dehydrogenase (ALDH) inhibitory drug disulfiram (DSF) was found to be a breast cancer-associated protein 2 (BCA2) inhibitor with potent antitumor activity. We herein describe our work in the synthesis and evaluation of new series of zinc-affinic molecules to explore the structural requirements for selective BCA2-inhibitory antitumor activity. An N(C - S)S - S motif was found to be required, based on selective activity in BCA2-expressing breast cancer cell lines and against recombinant BCA2 protein. Notably, the DSF analogs (3a and 3c) and dithio(peroxo)thioate compounds (5d and 5f) were found to have potent activity (submicromolar IC50) in BCA2 positive MCF-7 and T47D cells but were inactive (IC50 > 10 μM) in BCA2 negative MDA-MB-231 breast cancer cells and the normal breast epithelial cell line MCF10A. Testing in the isogenic BCA2 +ve MDA-MB-231/ER cell line restored antitumor activity for compounds that were inactive in the BCA2 -ve MDA-MB-231 cell line. In contrast, structurally related dithiocarbamates and benzisothiazolones (lacking the disulfide bond) were all inactive. Compounds 5d and 5f were additionally found to lack ALDH-inhibitory activity, suggestive of selective E3 ligase-inhibitory activity and worthy of further development.
