Yazar "Supuran C.T." seçeneğine göre listele

Listeleniyor 1 - 4 / 4
  • Küçük Resim Yok
    Öğe
    Analysis of saponins and phenolic compounds as inhibitors of ?-carbonic anhydrase isoenzymes
    (Informa Healthcare, 2014) Koz Ö.; Ekinci D.; Perrone A.; Piacente S.; Alankus-Caliskan Ö.; Bedir E.; Supuran C.T.
    A series of phenolic and saponin type natural products such as quercetin, rutin, catechin, epicatechin, silymarin, trojanoside H, astragaloside IV, astragaloside VIII and astrasieversianin X, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). We here report inhibitory effects of these compounds against five ?-CA isozymes (hCA I, hCA II, bCA III, hCA IV and hCA VI). Most of the phenolic and saponin type compounds inhibited the isoenzymes quite effectively at low micromolar KI-s ranging between 0.1 and 4 µM, whereas a few derivatives were ineffective (KI-s > 100 µM). The results were remarkable which might lead to design of novel CAIs with a diverse inhibition mechanism compared to sulfonamide/sulfamate inhibitors. © 2013 Informa UK, Ltd.
  • Küçük Resim Yok
    Öğe
    Handling drug-target selectivity: A study on ureido containing Carbonic Anhydrase inhibitors
    (Elsevier Masson s.r.l., 2021) Akgul O.; Singh S.; Andring J.T.; McKenna R.; Selleri S.; Carta F.; Supuran C.T.
    Here we report the synthesis of a series of taurine substituted sulfonamide derivatives 1-29 having the ureido moiety installed at the tail section as selective inhibitors of the tumor associated human (h) Carbonic Anhydrase (CA; EC 4.2.1.1) IX and XII. The series was deeply investigated for their kinetic features which demonstrated a strong dependence on the ureido moiety. High resolution X-ray crystallographic investigation on selected ligand adducts complexed with hCA II and hCA IX-mimic revealed a strong correlation between the ureido moiety and the amino acid residues Q92 and Q67 in both the hCA II and hCA IX-mimic, contributing to highly stabilized ligand-protein complex. © 2020 Elsevier Masson SAS
  • Küçük Resim Yok
    Öğe
    Pain relieving effect of-NSAIDS-CAIs hybrid molecules: Systemic and intra-articular treatments against rheumatoid arthritis
    (MDPI AG, 2019) Micheli L.; Bozdag M.; Akgul O.; Carta F.; Guccione C.; Bergonzi M.C.; Bilia A.R.; Cinci L.; Lucarini E.; Parisio C.; Supuran C.T.; Ghelardini C.; Di Cesare Mannelli L.
    To study new target-oriented molecules that are active against rheumatoid arthritis-dependent pain, new dual inhibitors incorporating both a carbonic anhydrase (CA)-binding moiety and a cyclooxygenase inhibitor (NSAID) were tested in a rat model of rheumatoid arthritis induced by CFA intra-articular (i.a.) injection. A comparison between a repeated per os treatment and a single i.a. injection was performed. CFA (50 µL) was injected in the tibiotarsal joint, and the effect of per os repeated treatment (1 mg kg-1) or single i.a injection (1 mg ml-1, 50 µL) with NSAIDs-CAIs hybrid molecules, named 4 and 5, was evaluated. The molecules 4 and 5, which were administered daily for 14 days, significantly prevented CFA-induced hypersensitivity to mechanical noxious (Paw pressure test) and non-noxious stimuli (von Frey test), the postural unbalance related to spontaneous pain (Incapacitance test) and motor alterations (Beam balance test). Moreover, to study a possible localized activity, 4 and 5 were formulated in liposomes (lipo 4 and lipo 5, both 1 mg ml-1) and directly administered by a single i.a. injection seven days after CFA injection. Lipo 5 decreased the mechanical hypersensitivity to noxious and non-noxious stimuli and improved motor coordination. Oral and i.a. treatments did not rescue the joint, as shown by the histological analysis. This new class of potent molecules, which is able to inhibit at the same time CA and cyclooxygenase, shows high activity in a preclinical condition of rheumatoid arthritis, strongly suggesting a novel attractive pharmacodynamic profile. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
  • Küçük Resim Yok
    Öğe
    Taurultams incorporating arylsulfonamide: First in vitro inhibition studies of ?-, ?- and ?-class Carbonic Anhydrases from Vibrio cholerae and Burkholderia pseudomallei
    (Elsevier Masson s.r.l., 2021) Akgul O.; Angeli A.; Selleri S.; Capasso C.; Supuran C.T.; Carta F.
    A new series of taurultambenzenesulfonamides 1–17 were prepared and considered for their inhibitory activity in vitro against the Carbonic Anhydrases from Vibrio cholerae (VchCA-?, VchCA-? and VchCA-?) and Burkholderia pseudomallei (BpsCA-? and BpsCA-?). Among the compounds tested, derivatives 4, 5, 7, 10, 12, and 16 resulted in highly effective VchCA? inhibitors (KI values spanning within the 6.1–9.6 nM range) and endowed with excellent Selectivity Indexes (SIs; KI VchCA-?/KI hCA II) all comprised between 0.04 and 0.09. Potent in vitro inhibitors for the BpsCA-? were also identified (KIs of 18.9–19.5 nM). The results here reported may represent the blueprint for the future development of a new generation of CA-based antibiotics integrated with free of resistance mechanisms of action adopted from known drugs. © 2021 Elsevier Masson SAS