Tellurides Bearing Sulfonamides as Novel Inhibitors of Leishmanial Carbonic Anhydrase with Potent Antileishmanial Activity

Angeli, Andrea; Etxebeste-Mitxeltorena, Mikel; Sanmartín, Carmen; Espuelas, Socorro; Moreno, Esther; Azqueta, Amaya; Parkkila, Seppo; Carta, Fabrizio

doi:10.1021/acs.jmedchem.0c00211

Cited by 26 publications

(16 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inhibition constants were obtained by non-linear least-squares methods using PRISM 3 and the Cheng-Prusoff equation as reported earlier and represent the mean from at least three different determinations. All CA isoforms were recombinant proteins obtained in house, as reported earlier 14 , 26–29 .…”

Section: Methodsmentioning

confidence: 99%

Development of Praziquantel sulphonamide derivatives as antischistosomal drugs

Angeli

Ferraroni

Carta

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

The almost empty armamentarium to treat schistosomiasis, a neglected parasitic disorder caused by trematode flatworms of the genus Schistosoma , except Praziquantel (PZQ), urged to find new alternatives to fight this infection. Carbonic Anhydrase from Schistosoma mansoni (SmCA) is a possible new target against this nematode. Here, we propose new PZQ derivatives bearing a primary sulphonamide group in order to obtain hybrid drugs. All compounds were evaluated for their inhibition profiles on both humans and Schistosoma CAs, X-ray crystal data of SmCA and hCA II in adduct with some inhibitors were obtained allowing the understanding of the main structural factors responsible of activity. The compounds showed in vitro inhibition of immature and adult S. mansoni , but further optimisation is required for improved activity.

show abstract

Section: Methodsmentioning

confidence: 99%

Development of Praziquantel sulphonamide derivatives as antischistosomal drugs

Angeli

Ferraroni

Carta

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…14,27 All CA isoforms were recombinant isoforms that were obtained in-house as previously reported. 14,27,28 5.2.2. Cell Culture, Metabolic Activity Assay, and Proliferation Assessment.…”

Section: Methodsmentioning

confidence: 99%

Mechanisms of the Antiproliferative and Antitumor Activity of Novel Telomerase–Carbonic Anhydrase Dual-Hybrid Inhibitors

et al. 2021

Self Cite

View full text Add to dashboard Cite

Human (h) telomerase (TL; EC 2.7.7.49) plays a key role in sustaining cancer cells by means of elongating telomeric repeats at the 3′ ends of chromosomes. Since TL-inhibitor (TI) stand-alone cancer therapy has been proven to be remarkably challenging, a polypharmacological approach represents a valid alternative. Here we consider a series of compounds able to inhibit both hTL and the tumor-associated carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII. Compounds 7 and 9 suppressed hTL activity in both cell lysates and human colon cancer cell lines, and prolonged incubation with either 7 or 9 resulted in telomere shortening, cell cycle arrest, replicative senescence, and apoptosis. Enzyme kinetics showed that 7 and 9 are mixed-type inhibitors of the binding of DNA primers and deoxynucleoside triphosphate (dNTP) to the TL catalytic subunit hTERT, which is in agreement with docking experiments. Compound 9 showed antitumor activity in Colo-205 mouse xenografts and suppressed telomerase activity by telomere reduction.

show abstract

“…In-vitro and in-vivo toxicity experiments have highlighted the innocuity of this compound. [17] This study provides new directions for the design and subsequent development of drug candidates targeting the carbonic anhydrase of Leishmania or more generally of other protozoan parasites.…”

Section: Highlighted By Jean-yves Winummentioning

confidence: 99%