Preparation of Two Maleic Acid Sulfonamide Salts and Their Copper(II) Complexes and Antiglaucoma Activity Studies

Two novel proton transfer compounds (HAP)+(SAMAL)- and (HBI)+(SAMAL)-.H2O were obtained from (E)-4-oxo-4-(4-sulfamoylphenylamino)but-2-enoic acid (HSAMAL) and 2-aminopyridine (AP) or 1H-benzimidazole (BI), respectively. Copper(II) complexes of salts and of HSAMAL have also been prepared. They have been characterized by elemental, spectral, thermal analyses, magnetic measurement and molar conductivity. Human carbonic anhydrase isozymes (hCA I and hCA II) were purified from erythrocytes by using affinity chromatography as 84.40 and 188.71 fold, respectively. The inhibitory effects of synthesized compounds and acetazolamide (AAZ, control compound) on the hydratase and esterase activities of hCA isozymes have been studied as in vitro to find out their antiglaucoma potentials. The inhibition constant (Ki) values of the compounds were in the range of 0.18 ± 0.007 to 10.24 ± 0.014 µmol L-1 for hCA I, and 0.12 ± 0.004 to 130.11 ± 0.021 µmol L-1 for hCA II

Synthesis and Structural Studies of Proton Transfer Salt Between Benzimidazole and (E)-4-oxo-4-(4-sulfamoylphenylamino)but-2-enoic Acid and Their Transition Metal Complexes, and Investigation of Inhibition Properties on hCAI and hCA II Isoenzymes

Bu çalışmada, ilk olarak sülfanilamit (sa) ve maleik anhidritin (mal) tepkimesinden (E)-3-(4- sülfamoyilfenil)amino)büt-2-enoik asit (Hsamal) bileşiği sentezlenmiş ve sonra bu bileşiğin 2-aminopiridin (ap) ile proton transfer tuzu (Hapsamal) hazırlanmıştır. Bu tuzun Fe(II), Co(II), Ni(II) ve Zn(II) geçiş metal kompleksleri sentezlenmiştir. Proton transfer tuzlarının yapısı elementel analiz, 1H-NMR, 13C-NMR, FT-IR, UV-Vis metotları ile aydınlatılmıştır. Amorf halde elde edilen geçiş metal komplekslerinin yapıları ise elementel analiz, ICP-OES, FT-IR, UV-Vis, manyetik duyarlılık ve molar iletkenlik sonuçları dikkate alınarak önerilmiştir. Ayrıca, sentezlenen maddelerin insan eritrosit hCA I ve hCA II izoenzimleri üzerindeki inhibisyon etkilerini belirlemek üzere in vitro çalışmalar yapılmıştır. Yeni sentezlenen maddelerin izoenzimlerin esteraz aktivitesini inhibe ettiği tespit edilmiştir. Bu maddelerin inhibisyon değerlerinin kontrol bileşiği asetazolamid (AAZ) değerleri ile kıyaslanabilir büyüklükte olduğu tespit edilmiştir.In this study, first (E)-4-oxo-4-(4-sulfamoylphenylamino)but-2-enoic acid (Hsamal) have been synthesized from the reaction between sulfanilamide (sa) and maleic anhydride (mal) and second, proton transfer salt (Hapsamal) has been prepared from 2-aminopyridine (ap) and Hsamal. Four transition metal complexes [Fe(II), Co(II), Ni(II) and Zn(II)] of the salt have also been synthesized. The structure of proton transfer compounds have been proposed by using elemantal analysis, 1H-NMR, 13C-NMR, FT-IR, UV-Vis techniques. The structure of amorphous metal complexes have been proposed by using elemantal analysis, ICP-OES, FT-IR, UV-Vis, magnetic susceptibility and molar conductivity techniques. In addition, in vitro studies have been performed to determine the inhibition effects of synthesized compounds on human erythrocyte hCA I and hCA II isoenzymes. It has been observed that synthesized compounds have affected esterase activities of hCA I and hCA II and the inhibition values of these compounds are comparable with the inhibition values of control compound acetazolamide (AAZ)

Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells highlighted “hsa-miR-2278” as a tumor suppressor for regain of chemotherapeutic imatinib response due to targeting STAT5A

BCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine kinase inhibitor, but developing chemotherapeutic resistance has to be overcome. In this study, we aimed to determine differing genome-wide microRNA (miRNA) and messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 μM) and parental cells by targeting STAT5A via small interfering RNA (siRNA) applications. After determining possible therapeutic miRNAs, we aimed to check their effects upon cell viability and proliferation, apoptosis, and find a possible miRNA::mRNA interaction to discover the molecular basis of imatinib resistance. We detected that miR-2278 and miR-1245b-3p were most significantly regulated miRNAs according to miRNome array. Upregulating miR-2278 expression resulted in the inhibition of resistant leukemic cell proliferation and induced apoptosis, whereas miR-1245b-3p did not exhibit therapeutic results. Functional analyses indicated that AKT2, STAM2, and STAT5A mRNAs were functional targets for miR-2278 as mimic transfection decreased their expressions both at transcriptional and translational level, thus highlighting miR-2278 as a tumor suppressor. This study provides new insights in discovering the mechanism of imatinib resistance due to upregulating the tumor-suppressor hsa-miR-2278 which stands for a functional therapeutic approach, inhibited leukemic cell proliferation, induced apoptosis, and regain of chemotherapeutic drug response in CML therapy. © 2015, International Society of Oncology and BioMarkers (ISOBM).Ege University Research Fund (APAK 2013-TIP/083

Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells highlighted “hsa-miR-2278” as a tumor suppressor for regain of chemotherapeutic imatinib response due to targeting STAT5A

BCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine kinase inhibitor, but developing chemotherapeutic resistance has to be overcome. In this study, we aimed to determine differing genome-wide microRNA (miRNA) and messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 μM) and parental cells by targeting STAT5A via small interfering RNA (siRNA) applications. After determining possible therapeutic miRNAs, we aimed to check their effects upon cell viability and proliferation, apoptosis, and find a possible miRNA::mRNA interaction to discover the molecular basis of imatinib resistance. We detected that miR-2278 and miR-1245b-3p were most significantly regulated miRNAs according to miRNome array. Upregulating miR-2278 expression resulted in the inhibition of resistant leukemic cell proliferation and induced apoptosis, whereas miR-1245b-3p did not exhibit therapeutic results. Functional analyses indicated that AKT2, STAM2, and STAT5A mRNAs were functional targets for miR-2278 as mimic transfection decreased their expressions both at transcriptional and translational level, thus highlighting miR-2278 as a tumor suppressor. This study provides new insights in discovering the mechanism of imatinib resistance due to upregulating the tumor-suppressor hsa-miR-2278 which stands for a functional therapeutic approach, inhibited leukemic cell proliferation, induced apoptosis, and regain of chemotherapeutic drug response in CML therapy. © 2015, International Society of Oncology and BioMarkers (ISOBM).Ege University Research Fund (APAK 2013-TIP/083