Inhibition of carbonic anhydrase isozymes I and II with natural products extracted from plants, mushrooms and honey (original) (raw)
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Investigation of The Effects of Some Edible Mushroom Extracts on Human Carbonic Anhydrase Isozymes
2015
Bu çalışmada, dört yenebilir mantar türünün (Lentinula edodes, Lactarius deliciosus, Lactarius deterrimus, Terfezia boudieri) insan karbonik anhidraz izoenzimleri (hCA I ve hCA II) üzerine etkileri in vitro olarak incelenmiştir. hCA I ve II izoenzimleri Sepharose4B-L-tirozin-p-aminobenzen sülfonamit afinite kromatografisi kullanılarak eritrositlerden saflaştırıldı. Daha sonra mantar özütlerinin hCA I ve II izoenzimlerinin hidrataz ve esteraz aktivitelerinin üzerine etkileri ölçüldü. L. edodes hCA I ve II nin esteraz aktiviteleri üzerinde inhibitor etki göstermiştir. Ancak diğer özütler hCA I ve II nin esteraz aktiviteleri üzerinde aktivatör etki göstermişlerdir.
Carbonic Anhydrase I and II Inhibition with Natural Products: Leucas cephalotes
2011
Carbonic anhydrases (EC 4.2.1.1) are ubiquitous metalloenzymes present in prokaryotes and eukaryotes that are encoded by five evolutionarily unrelated gene families are involved in numerous physiological and pathological processes. Novel interesting chemo types, in addition to the sulphonamide and sulfamate were discovered, many of which are based on natural products, such as phenols/polyphenols, phenolic acids, and coumarins. Methanolic extract of Leucas cephalotes belongs to family Labiatae (or Lamiaceae) tested for human carbonic anhydrase (hCA) I and II inhibition study. The significant IC 50 values are calculated for the methanolic extract of Leucas cephalotes for hCA I found to be 0.23 mM/ml which is showing relatively less potent then hCA inhibition against hCA II having IC 50 values of 0.19 mM/ml. Leucas cephalotes is a weak inhibitors they may constitute leads for developing tighter binding compounds.
Journal of enzyme inhibition and medicinal chemistry, 2016
Polyphenols are important secondary products of plants with the potential to inhibit carbonic anhydrases. The aim of this study was to investigate the inhibition effects of various phenolic standards, honey, propolis, and pollen species on human carbonic anhydrase I and II. The inhibition values (IC50) of the phenolics (gallic acid, protocatechuic acid, quercetin, catechin, tannic acid, and chrysin) ranged from 0.009 to 0.32 μg/mL, tannic acid emerging as the best inhibitor. The inhibition values of three different types of honey, heather, rhododendron, and chestnut ranged between 2.32 and 25.10 μg/mL, the chestnut honeys exhibiting the best inhibition. The ethanolic extracts of pollen and propolis exhibited good inhibitory properties, with IC50 values between 0.486 and 3.320 μg/mL. In order to evaluate the phenolic composition of bee products, phenolic profiles and total phenolic contents (TFC) were also measured. The inhibition ranking among the natural products studied was phenol...
Journal of Obesity & Metabolic Syndrome
Background: Human carbonic anhydrases (CAs) play a role in various pathological mechanisms by controlling intracellular and extracellular pH balance. Irregular expression and function of CAs have been associated with multiple human diseases, such as obesity, cancer, glaucoma, and epilepsy. In this work, we identify herbal compounds that are potential inhibitors of CA VI. Methods: We used the AutoDock tool to evaluate binding affinity between the CA VI active site and 79 metabolites derived from flavonoids, anthraquinones, or cinnamic acids. Compounds ranked at the top were chosen for molecular dynamics (MD) simulations. Interactions between the best CA VI inhibitors and residues within the CA VI active site were examined before and after MD analysis. Additionally, the effects of the most potent CA VI inhibitor on cell viability were ascertained in vitro through the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Results: Kaempferol 3-rutinoside-4-glucoside, orientin, kaempferol 3-rutinoside-7-sophoroside, cynarin, and chlorogenic acid were estimated to establish binding with the CA VI catalytic domain at the picomolar scale. The range of root mean square deviations for CA VI complexes with kaempferol 3-rutinoside-4-glucoside, aloe-emodin 8-glucoside, and cynarin was 1.37 to 2.05, 1.25 to 1.85, and 1.07 to 1.54 Å, respectively. The MTT assay results demonstrated that cynarin had a substantial effect on HCT-116 cell viability. Conclusion: This study identified several herbal compounds that could be potential drug candidates for inhibiting CA VI.
Journal of Enzyme Inhibition and Medicinal Chemistry, 2014
Carbonic anhydrases (CAs) are widespread metalloenzymes in higher vertebrates including humans. A series of phenolic compounds, including guaiacol, 4-methylguaiacol, 4-propylguaiacol, eugenol, isoeugenol, vanillin, syringaldehyde, catechol, 3-methyl catechol, 4-methyl catechol and 3-methoxy catechol were investigated for their inhibition of all the catalytically active mammalian isozymes of the Zn 2+-containing CA (EC 4.2.1.1). All the phenolic compounds effectively inhibited human carbonic anhydrase isoenzymes (hCA I, II, IX and XII), with K i s in the range of 2.20-515.98 lM. The various isozymes showed diverse inhibition profiles. Among the tested phenolic derivatives, compounds 4-methyl catechol and 3-methoxy catechol showed potent activity as inhibitors of the tumour-associated transmembrane isoforms (hCA IX and XII) in the submicromolar range, with high selectivity. The results obtained from this research may lead to the design of more effective carbonic anhydrase isoenzyme inhibitors (CAIs) based on such phenolic compound scaffolds.
The in Vitro Impacts of Some Plant Extracts on Carbonic Anhydrase I, II and PARAOXONASE-1
Hacettepe Journal of Biology and Chemistry, 2019
B u makale insan karbonik anhidraz (CA) izoformları hCAI, hCAII ve paraoksonaz-1 (PON1) aktiviteleri üzerine bitki özütlerinin in vitro inhibisyonlarına odaklanmaktadır. Bu çalışmada beş farklı bitki (Alcea rosea, Foeniculum vulgare, Elettaria cardamomum, Laurus azorica and Lavandula stoechas) seçildi. Bitkilerin metanol, etanol ve su özütleri hazırlandı ve hCA I, II izoenzimleri ve hPON1 için derişime bağlı inhibisyon dereceleri spektrofotometrik olarak bulundu. Böylece her bir özüt için IC 50 (mg/mL) değerleri belirlendi. Elettaria cardamomum'un metanol özütü en yüksek inhibisyon etkisine (0.032 mg/mL) sahipti. Bitkilerin su özütleri metanol ve etanol ekstreleri ile kıyaslandığında daha düşük inhibitor etkisi gösterdi.
Screening and docking studies of natural phenolic inhibitors of carbonic anhydrase II
Science in China Series B: Chemistry, 2009
Carbonic anhydrase Ⅱ (CAⅡ) is an important enzyme complex with Zn 2+ ，which is involved in many physiological and pathological processes, such as calcification, glaucoma and tumorigenicity. In order to search for novel inhibitors of CAⅡ, inhibition assay of carbonic anhydrase Ⅱ was performed, by which seven natural phenolic compounds, including four phenolics (grifolin, 4-O-methyl-grifolic acid, grifolic acid, and isovanillic acid) and three flavones (eriodictyol, quercetin and puerin A), showed inhibitory activities against CAⅡ with IC 50 s in the range of 6.37-71.73 μmol/L. Grifolic acid is the most active one with IC 50 of 6.37 μmol/L. These seven phenolic compounds were proved to be novel natural carbonic anhydrase Ⅱ inhibitors, which were obtained in flexible docking study with GOLD 3.0 software. Results indicated that the aliphatic chain and polar groups of hydroxyl and carboxyl are important to their inhibitory activities, providing a new insight into study on CA Ⅱ potent inhibitors.
Phenols and Polyphenols as Carbonic Anhydrase Inhibitors
Molecules, 2016
Phenols are among the largest and most widely distributed groups of secondary metabolites within the plant kingdom. They are implicated in multiple and essential physiological functions. In humans they play an important role as microconstituents of the daily diet, their consumption being considered healthy. The physical and chemical properties of phenolic compounds make these molecules versatile ligands, capable of interacting with a wide range of targets, such as the Carbonic Anhydrases (CAs, EC 4.2.1.1). CAs reversibly catalyze the fundamental reaction of CO 2 hydration to bicarbonate and protons in all living organisms, being actively involved in the regulation of a plethora of patho/physiological processes. This review will discuss the most recent advances in the search of naturally occurring phenols and their synthetic derivatives that inhibit the CAs and their mechanisms of action at molecular level. Plant extracts or mixtures are not considered in the present review.
Recent advances in the medicinal chemistry of carbonic anhydrase inhibitors
European Journal of Medicinal Chemistry, 2021
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