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Carbon Dioxide Sequestration by Microalgae
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
G.V. Swarnalatha, Ajam Shekh, P.V. Sijil, C.K. Madhubalaji, Vikas Singh Chauhan, Ravi Sarada
RuBisCO is known to have both competitive carboxylase and oxygenase functions. The two competitive reactions of RuBisCO in autotrophic cells depend on the concentrations of O2 and CO2 at active site of the RuBisCO. The relative rates of carboxylase and oxygenase reactions are calculated by selectivity factor (Equation 6.3).
Basics Of Gas Chromatography Mass Spectrometry System
Published in Raquel Cumeras, Xavier Correig, Volatile organic compound analysis in biomedical diagnosis applications, 2018
William Hon Kit Cheung, Raquel Cumeras
The polarity of the analytical GC column is a function of the stationary phase’s chemical composition, and the selection of the appropriate column for a particular application is dictated by both the polarity of the target compounds and the GC column’s stationary phase composition. If the stationary phase and the target compounds have comparable polarities, this will result in a strong retention interaction; higher column retention generally equates to greater chromatographic separation and higher resolution. The polarity of the stationary phase will also strongly influence column selectivity and separation. The selectivity factor (α) can be directly related to the stationary phase composition, giving rise to subsequent interaction with the target compounds via intermolecular forces such as hydrogen bonding and dipole–dipole interaction. The effect of temperature is also an important consideration as high polarity stationary phase generally has a lower maximum operating temperature limit (Agilent, 2016; Restek, 2016).
Direct measurement of light and heavy antibody chains using ion mobility and middle-down mass spectrometry
Published in mAbs, 2019
Rafael D. Melani, Kristina Srzentić, Vincent R. Gerbasi, John P. McGee, Romain Huguet, Luca Fornelli, Neil L. Kelleher
where n is the number of theoretical plates, α the selectivity factor, and k the retention factor.38 For optimal characterization of mAb chains targeted LC-MS/MS, full separation (high selectivity) between species is desirable, but this is typically associated with narrow elution peaks (high efficiency), limiting the number of MS/MS scans that can be acquired. Under ideal conditions for ultra-high-pressure liquid chromatography, Lc and Hc are separated in about 6–7 min,39 although generally 10–15 min gradients are necessary for higher quality MS/MS datasets to be acquired during peak elution off the column. Further, multiple LC runs are needed to obtain good fragmentation data using different ion-activation techniques.
A patent review of aldosterone synthase inhibitors (2014-present)
Published in Expert Opinion on Therapeutic Patents, 2022
Table 1 summarizes the ASI that have been under clinical development according to searches of the Scifinder, Cortellis, and Adis-insight databases, with regard to their structure, indication, and development status. As shown, most of the clinical trials have been discontinued or have failed to report any developments with respect to the treatment of hypertension, heart failure, and cardiovascular disorders, with the exception of DP13 and CIN-107. Both compounds were progressed into Phase II clinical trials in 2020 for the treatment of hyperaldosteronism, and hyperaldosteronism and spinal cord disorders, respectively. FAD286 (1) is a R-enantiomer of Fadrozole, a nonsteroidal aromatase (CYP19) inhibitor that has been used in Japan for the treatment of breast cancer. Clinical observations suggest that it affects aldosterone levels, with subsequent studies suggesting it is a potent ASI [31]. LCI699, a close analog of FAD286, was the first clinical PoC ASI for the treatment of primary aldosteronism (PA). After oral administration of LCI699, firstly at 0.5 mg b.i.d. for two weeks and thereafter at 1.0 mg b.i.d. for a further two weeks, aldosterone levels in both plasma and urine were significantly reduced, resulting in a rapid correction of hypokalemia, and a modest decrease in blood pressure [32,33]. Not surprisingly, the ACTH-stimulated cortisol response suppression effect was also observed at a dose of 1 mg/day due to a low selectivity over hCYP11B1 (hCYP11B2 IC50 = 0.7 nM and hCYP11B1 IC50 = 2.5 nM). Hence, this compound was precluded for the treatment of hypertension and heart failure, but was approved for the treatment of Cushing’s disease, a condition caused by excessive levels of the hormone, cortisol [34]. Later on, Novartis progressed another structurally distinct compound, LLF269, to clinical study to treat essential hypertension [35]. Even with much improved selectivity over hCYP11B1 with a selectivity factor (SF) of 100, the phase II trial was terminated also, due to unknown reasons. In 2017, Roche reported the preclinical and early clinical profile of RO6836191 (structure undisclosed), a highly selective, potent and oral ASI with a Ki value of 13 nM against hCYP11B2 and an SF of >100 over hCYP11B1 [36]. In healthy subjects, single-dose administration of this compound decreased plasma aldosterone response in a dose-dependent manner with the maximum effect reached at 10 mg with no effect on plasma cortisol. Another two phase I trials were disclosed by Eli Lilly for LY3045697, which has an IC50 of 4.5 nM against hCYP11B2 and an SF of 39 over hCYP11B1 [37]. Similarly, this compound demonstrated a dose-dependent decrease in plasma and urine aldosterone.
S-substituted 2-mercaptoquinazolin-4(3H)-one and 4-ethylbenzensulfonamides act as potent and selective human carbonic anhydrase IX and XII inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Adel S. El-Azab, Alaa A.-M. Abdel-Aziz, Silvia Bua, Alessio Nocentini, Nawaf A. AlSaif, Mohammed M. Alanazi, Manal A. El-Gendy, Hany E. A. Ahmed, Claudiu T. Supuran
The CA inhibitory activity of 4-(2-(2-(substituted-thio)-4(3H)-quinazolinon-3-yl)ethyl)benzenesulfonamides (compounds 2–20) towards hCA I, II, IV, and IX isoforms was measured and compared to acetazolamide (AAZ), a typical sulphonamide inhibitor. hCA I was effectively inhibited by compounds 2 and 4–13 with the inhibition-constant (KI) values ranging from 114.5–938.3 nM (AAZ: KI = 250.0 nM). Compounds 3 and 16 showed moderate activity with KI values of 1447.0 and 1697.0 nM, respectively, while compounds 14–15 and 17–20 showed weak activity with KI values ranging from 2048–5467 nM. Compounds 5, 8, 9, 11, 12, and 20 were verified to be effective hCA II inhibitors, with KI values of 25.4–95.4 nM (AAZ: KI = 12.0 nM). Compounds 2, 3, 4, 6, 7, 10, 14, and 16 showed modest hCA II inhibitory activity with KI values ranging between 116.2 and 266.1 nM, whereas compounds 13 and 15 showed a weak inhibitory activity with KI values of 304.6 and 1099.0 nM, respectively. Compounds 2–17 and 20 displayed potent hCA IX inhibitory activity with KI values ranging from 8.0 to 100.4 nM, which were greater than or nearly identical to that of AAZ (KI = 25.0 nM), whereas compounds 18 and 19 showed modest hCA IX inhibitory activity with KI values ranging between 256.4 and 145.1 nM, respectively. 4-(2-(2-(Substituted-thio)-4(3H)-quinazolinon-3-yl)ethyl)benzenesulfonamide derivatives 2, 4, 5, 8, 9, 11, 12, 13, 14, 16 and 17 showed potent hCA XII inhibitory activity with KI values of 2.4–49.1 nM compared to AAZ (KI = 5.7 nM), whereas compounds 3, 6, 7, 10, 15, 18, 19, and 20 exerted moderate hCA XII inhibitory activities with KI values of 59.7–113.4 nM (Table 1). On the other hand, the selectivity factor is critical goal to increase the value of the new synthesised compounds. New compounds, such as 2 and 4 showed characteristic effective and selective antitumor (hCA IX and hCA XII) carbonic anhydrase inhibitory activity with KI values (compound 2; 40.7 and 13.0 nM) and KI values (compound 4; 8.0, and 10.8 nM) compared with AAZ (KI values of 25 and 5.7 respectively). 4-(2-(2-((2-(4-Substituted-phenyl)-2-oxoethyl)thio)-4-oxoquinazolin-3(4H)-yl)ethyl)benzenesulfonamides (compounds 2–7) showed high selectivity in the inhibition of hCA IX over hCA I and hCA II (in the range of 15.0–95.0 and 2.3–23.0, respectively), as well as selectivity in the inhibition of hCA XII over hCA I and hCA II (in the range of 5.5–70.0 and 2.5–17.0, respectively) (Table 1).