Abstract:
:An expanded set of diversely substituted 1,2,4-oxadiazole-containing primary aromatic sulfonamides was synthesized and tested for inhibition of human carbonic anhydrase I, II, IX and XII isoforms. The initial biochemical profiling revealed a significantly more potent inhibition of cancer-related, membrane-bound isoform hCA IX (reaching into submicromolar range), on top of potent inhibition of hCA XII that is another cancer target. The observed structure-activity relationships have been rationalized by molecular modeling. Comparative single-concentration profiling of the carbonic anhydrase inhibitors synthesized for antiproliferative effects against normal (ARPE-19) and cancer (PANC-1) cell lines under chemically induced hypoxia conditions revealed several candidate compounds selectively targeting cancer cells. More in-depth characterization of these leads revealed two structurally related compounds that showed promising selective cytotoxicity against pancreatic cancer (PANC-1) and melanoma (SK-MEL-2) cell lines.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Krasavin M,Shetnev A,Sharonova T,Baykov S,Kalinin S,Nocentini A,Sharoyko V,Poli G,Tuccinardi T,Presnukhina S,Tennikova TB,Supuran CTdoi
10.1016/j.ejmech.2018.12.049subject
Has Abstractpub_date
2019-02-15 00:00:00pages
92-105eissn
0223-5234issn
1768-3254pii
S0223-5234(18)31087-0journal_volume
164pub_type
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