Fluorescence spectroscopy in a study of anticancer drugs: 7-tert-butyldimethylsilyl-camptothecin and 7-tert-butyldimethylsilyl-10-[4- (1-piperidino)-1-piperidino]-carbonyloxycamptothecin

Background. Camptothecin (CPT), an alkaloid isolated from the Chinese tree Camptotheca acuminata,exhibits very high anticancer activity. CPT is a fluorescent compound and this is a very useful property. Using methods of fluorescence spectroscopy, one can determine or predict the biophysical propertiesof this promising compound. The cellular target of CPT is topoisomerase I. CPT interacts only with thosecells which are in the S-phase. CPT molecules bind to topoisomerase I – DNA complex and prevent thereplication process. This means that CPT is toxic to those cells that are undergoing DNA synthesis. Cancerouscells are rapidly replicating and they spend more time in the S-phase in relation to healthy tissues,and therefore they are killed with much higher efficiency than the healthy host tissues. Such selectivity ofcytotoxicity is a promising property of CPT. Due to the S-phase specificity of CPT, a continuous exposureto this drug must be maintained in order to achieve optimum therapeutic efficacy.Materials and methods. We used fluorescence anisotropy measurements to determine the properties ofbinding to membranes and proteins of two anticancer agents: 7-tert-butyldimethylsilyl-camptothecin and7-tert-butyldimethylsilyl- 10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin. The samples of CPT, 1Si-CPT and 2Si-CPT were obtained from the laboratory of biotechnology, College of Pharmacy, Universityof Kentucky, Lexington, USA. 2 mM stock solutions of CPT, 1Si-CPT and 2Si-CPT were prepared in DMSO.As model membranes, small unilamelar liposomes formed by DMPC and DMPG lipids were used.Results. Fluorescence anisotropy measurements prove that this new camptothecin analogue exhibitsdesirable properties: high affinity of lactone form to membranes and low affinity of carboxylate form toHSA. Such properties should ensure high stability of this drug in physiological fluids, including blood.The second considered compound, 7-tert-butyldimethylsilyl- camptothecin, exhibits very high affinity of itslactone form to membranes, but its carboxylate form exhibits also high affinity to HSA. The latter propertyexcludes this compound as a candidate to be a good anticancer drug.Conclusions. Fluorescence anisotropy measurements show that the lactone forms of 1Si-CPT and 2Si-CPTexhibit a high affinity to membranes but only the carboxylate form of 2Si-CPT behaves in a desirable way inHSA solution i.e. it exhibits a low affinity to this protein. This means that 2Si-CPT could be an excellent candidatefor further in vivo pharmacological studies, and most probably for clinical trials in cancer chemotherapy.Background. Camptothecin (CPT), an alkaloid isolated from the Chinese tree Camptotheca acuminata,exhibits very high anticancer activity. CPT is a fluorescent compound and this is a very useful property. Using methods of fluorescence spectroscopy, one can determine or predict the biophysical propertiesof this promising compound. The cellular target of CPT is topoisomerase I. CPT interacts only with thosecells which are in the S-phase. CPT molecules bind to topoisomerase I – DNA complex and prevent thereplication process. This means that CPT is toxic to those cells that are undergoing DNA synthesis. Cancerouscells are rapidly replicating and they spend more time in the S-phase in relation to healthy tissues,and therefore they are killed with much higher efficiency than the healthy host tissues. Such selectivity ofcytotoxicity is a promising property of CPT. Due to the S-phase specificity of CPT, a continuous exposureto this drug must be maintained in order to achieve optimum therapeutic efficacy.Materials and methods. We used fluorescence anisotropy measurements to determine the properties ofbinding to membranes and proteins of two anticancer agents: 7-tert-butyldimethylsilyl-camptothecin and7-tert-butyldimethylsilyl- 10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin. The samples of CPT,1Si-CPT and 2Si-CPT were obtained from the laboratory of biotechnology, College of Pharmacy, Universityof Kentucky, Lexington, USA. 2 mM stock solutions of CPT, 1Si-CPT and 2Si-CPT were prepared in DMSO.As model membranes, small unilamelar liposomes formed by DMPC and DMPG lipids were used.Results. Fluorescence anisotropy measurements prove that this new camptothecin analogue exhibitsdesirable properties: high affinity of lactone form to membranes and low affinity of carboxylate form toHSA. Such properties should ensure high stability of this drug in physiological fluids, including blood.The second considered compound, 7-tert-butyldimethylsilyl- camptothecin, exhibits very high affinity of itslactone form to membranes, but its carboxylate form exhibits also high affinity to HSA. The latter propertyexcludes this compound as a candidate to be a good anticancer drug.Conclusions. Fluorescence anisotropy measurements show that the lactone forms of 1Si-CPT and 2Si-CPTexhibit a high affinity to membranes but only the carboxylate form of 2Si-CPT behaves in a desirable way inHSA solution i.e. it exhibits a low affinity to this protein. This means that 2Si-CPT could be an excellent candidatefor further in vivo pharmacological studies, and most probably for clinical trials in cancer chemotherapy

Badanie właściwości antyoksydacyjnych flawonoidów oraz miodów metodami spektroskopii optycznej

Flavonoids are considered very efficient radical scavengers and found in almost every plant. Antioxidant activities of flavonoids and a few popular kinds of bee honeys were investigated using absorbance spectroscopy. Spectral methods are powerful tools for the study of biologically active compounds and allow measurements of low concentrated substances under physiological conditions. Quercetin, naringenin, catechin, 3-hydroxyflavone were studied during the reaction with the 2,2-diphenyl-1- picrylhydrazyl radical (DPPH·). The results suggest that quercetin and catechin are better antioxidants than vitamin C. Among the analyzed honeys buckwheat honey exhibited the strongest antioxidant properties. Kinetic studies of the radical-scavenging activity were also performed. One can observe that popular vitamin C reduces free radicals instantly after adding to the solution, while flavonoids cause rather an exponential decay in concentration of the free radicals in the solutions. Our results show that adding of CuCl2 to the solution of DPPH and quercetin did not influence the level of antioxidant capacity of quercetin.Flawonoidy uważane są za bardzo skuteczne wymiatacze wolnych rodników i występują niemal w każdej roślinie. Właściwości antyoksydacyjne flawonoidów oraz kilku najbardziej popularnych rodzajów miodów pszczelich zbadano metodami spektroskopii absorpcyjnej. Metody optyczne są przydatnym narzędziem do badania związków biologicznie czynnych i umożliwiają pomiary w niskich stężeniach badanych substancji oraz w warunkach fizjologicznych. Kwercetynę, naringeninę, katechinę, 3- hydroksyflawon badano w reakcji z rodnikiem 2,2-diphenyl- 1-picrylhydrazyl (DPPH•). Wyniki pokazują, że kwercetyna oraz katechina są lepszymi przeciwutleniaczami niż witamina C. Spośród analizowanych miodów miód gryczany wykazuje najsilniejsze właściwości antyoksydacyjne. Przeprowadzono także badania kinetyki wymiatania wolnych rodników. Zaobserwowano, że popularna witamina C wymiata wolne rodniki niemal natychmiast po dodaniu do roztworu DPPH, zaś flawonoidy raczej wywołują wykładniczy zanik stężenia wolnych rodników. Nasze wyniki wskazują także, że dodanie CuCl2 do roztworu DPPH i kwercetyny nie wpływa znacząco na zdolności przeciwutleniające kwercetyny

Antioxidant Properties of Flavonoids and Honeys Studied By Optical Spectroscopy Methods

Flavonoids are considered very efficient radical scavengers and found in almost every plant. Antioxidant activities of flavonoids and a few popular kinds of bee honeys were investigated using absorbance spectroscopy. Spectral methods are powerful tools for the study of biologically active compounds and allow measurements of low concentrated substances under physiological conditions. Quercetin, naringenin, catechin, 3-hydroxyflavone were studied during the reaction with the 2,2-diphenyl-1- picrylhydrazyl radical (DPPH·). The results suggest that quercetin and catechin are better antioxidants than vitamin C. Among the analyzed honeys buckwheat honey exhibited the strongest antioxidant properties. Kinetic studies of the radical-scavenging activity were also performed. One can observe that popular vitamin C reduces free radicals instantly after adding to the solution, while flavonoids cause rather an exponential decay in concentration of the free radicals in the solutions. Our results show that adding of CuCl 2 to the solution of DPPH and quercetin did not influence the level of antioxidant capacity of quercetin.Flawonoidy uważane są za bardzo skuteczne wymiatacze wolnych rodników i występują niemal w każdej roślinie. Właściwości antyoksydacyjne flawonoidów oraz kilku najbardziej popularnych rodzajów miodów pszczelich zbadano metodami spektroskopii absorpcyjnej. Metody optyczne są przydatnym narzędziem do badania związków biologicznie czynnych i umożliwiają pomiary w niskich stężeniach badanych substancji oraz w warunkach fizjologicznych. Kwercetynę, naringeninę, katechinę, 3- hydroksyflawon badano w reakcji z rodnikiem 2,2-diphenyl- 1-picrylhydrazyl (DPPH•). Wyniki pokazują, że kwercetyna oraz katechina są lepszymi przeciwutleniaczami niż witamina C. Spośród analizowanych miodów miód gryczany wykazuje najsilniejsze właściwości antyoksydacyjne. Przeprowadzono także badania kinetyki wymiatania wolnych rodników. Zaobserwowano, że popularna witamina C wymiata wolne rodniki niemal natychmiast po dodaniu do roztworu DPPH, zaś flawonoidy raczej wywołują wykładniczy zanik stężenia wolnych rodników. Nasze wyniki wskazują także, że dodanie CuCl 2 do roztworu DPPH i kwercetyny nie wpływa znacząco na zdolności przeciwutleniające kwercetyny

Comparison of high -performance thin layer chromatography/UV-densitometry and UV-derivative spectrophotometry for determination of trimetazidine in pharmaceutical formulation

New methods for assaying trimetazidine dihydrochloride on the basis of thin layer chromatography and spectrophotometry are proposed and compared in the paper. In HPTLC/UV-densitometry, separation is achieved by using a mobile phase composed of ammonia-methanol (30:70, V/V) on silica gel HPTLC plates F254. Quantification using a non-linear calibration curve is accomplished by densitometric detection at 230 nm. Derivative spectrophotometric determination of trimetazidine dihydrochloride is carried out from the fourth derivative of the absorbance at 233 nm in peak-zero mode. Statistical comparison led to the conclusion that there is no significant difference between the two studied methods and, moreover, that they demonstrate satisfactory accuracy and precision for routine applications

Fluorescence lifetime of collagen degradation products in plasma of patients with left ventricular remodeling

Background. The concentration of collagen degradation products in plasma may reflect the process of left ventricular remodeling in patients after acute myocardial infarction. The aim of this study was to confirm that mean fluorescence lifetime of plasma is decreased in patients with left ventricular systolic dysfunction. Patients, materials and methods. The study group consisted of patients treated with primary percutaneous coronary intervention for acute myocardial infarction admitted to the Department of Cardiology and Internal Medicine at the University Hospital in Bydgoszcz. The overall group comprised of 65 patients. From each patient 8 mL of blood was taken to obtain plasma that was used for further examination. The time-resolved spectrometer Life Spec II with the sub-nanosecond pulsed 360 nm EPLED® diode was used in order to measure fluorescence lifetime of samples. Results. Significant differences were observed in mean fluorescence lifetime of plasma between groups of patients divided according to brain natriuretic peptide levels. Statistical analysis showed that the increase in brain natriuretic peptide level is an independent factor resulting in the decrease in mean fluorescence lifetime. Conclusions. It seems that plasma concentration of collagen degradation products is closely related to brain natriuretic peptide level. However, this experiment confirmed that plasma of patients with potential high probability of developing left ventricular remodeling is characterized by the decrease in mean fluorescence lifetime

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License