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A series of new 1,ω-bis-(5-alkyl-3-tosyl-1,3,4,2-triazaphospholino)alkanes 2 and 3 were obtained in excellent yields by the condensation of 1,ω-bis-(1-tosylamidrazone)alkanes 1 with two equivalent molars of Lawesson's Reagent (LR) and trisdimethylaminophosphine, respectively. All synthesized compounds were characterized by various spectroscopic techniques including IR, 1 H NMR, 13 C NMR and 31 P NMR and elemental analysis. The newly synthesized compounds were evaluated against key enzymes related to diabetes and obesity such as α-amylase and lipase. This study showed that the compounds 3a and 2b are an excellent inhibitor of α-amylase (with IC 50  = 18.8 mM) and lipase (with IC 50  = 19 mM) respectively, as compared with standard, orlistat (IC 50  = 22 mM). Among this series, compounds 3a and 2b with the CH 3 or C 2 H 5 group at position 6 were identified as the most potent inhibitors against α-amylase, and lipase enzymes. The remaining compounds were found to be moderately active. Further, molecular docking simulation studies were done to identify the interactions and binding mode of synthesized analogs at binding site of α-amylase and lipase enzymes., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The Kingdom of Saudi Arabia was one of the first countries to implement a COVID-19 vaccination program. This study estimated the safety and reactogenicity of the ChAdOx1-S vaccine after the first dose administered to adults., Methods: This cross-sectional study included 1592 randomly selected vaccinees from April to May 2021. A questionnaire was delivered to the vaccinees via phone calls 7 and 21 days after the first vaccine dose., Results: Of the 1592 vaccinees who had the first dose, the mean age was 37.4 (± 9.6) years and 81% were males. Of all the vaccinees, 553 (34.7%) reported an adverse reaction on the first telephone call. The most common symptoms were: pain at the site of injection (485, 30.5%), musculoskeletal symptoms (438, 27.5%), skin rash (307, 19.2%), gastrointestinal symptoms (379, 23.8%) and fever (498, 31.3%). Men were more likely to report fever (76.9% vs. 23.1%; P = 0.005), skin rash (81.1% vs. 18.9%, P = 0.005) and pain at the injection site (77.3% vs. 22.7%, P < 0.0001). Post-vaccine COVID-19 infection was 0.5% and there were no hospitalizations., Conclusion: This study observed no major side effects of the ChAdOx1-S vaccine and no reported breakthrough infection during the observation period., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Integral membrane proteins PEPT1 and PEPT2 are essential for reabsorbing almost all hydrolysed or filtered di- and tripeptides alongside a wide range of peptidomimetic drugs in the kidney. The aim of this study was to investigate the potential use of the fluorophore-conjugated dipeptide β-Ala-Lys (AMCA) as a biosensor for measuring peptide transport activity in brush border membrane vesicles isolated from the outer cortex (BBMV-OC) and outer medulla (BBMV-OM) (representing PEPT1 and PEPT2 respectively). The vesicles were isolated using a dual magnesium precipitation and centrifugation technique. Intravesicular fluorescence accumulation was measured after incubating extra-vesicular media at pH6.6 and different concentrations of β-Ala-Lys (AMCA) with vesicles pre-equilibrated at pH7.4. Both BBMV-OC and BMMV-OM showed accumulation of an intravesicular fluorescence signal after 20min incubation. Changing the extra-vesicular pH to 7.4 caused a significant reduction in the β-Ala-Lys (AMCA) uptake into BBMV-OC at concentrations >100μM. When different concentrations of dipeptide, Gly-Gln was added, there was a significant inhibition of 100μM β-Ala-Lys (AMCA) uptake into BBMV-OC and BMMV-OM, reaching 69% and 80%, respectively. Kinetic analysis of β-Ala-Lys (AMCA) at 20min showed that the K m and V max were 783.7±115.7μM and 2191.2±133.9ΔF/min/mg for BBMV-OC, while BMMV-OM showed significantly higher affinity, but lower capacity at K m =93.6±21.9μM and V max =935.8±50.2ΔF/min/mg. These findings demonstrate the applicability of β-Ala-Lys (AMCA) as a biosensor to measure the transport activity of the renal-type PEPT1 and PEPT2 in BBMV-OC and BMMV-OM respectively., (Copyright © 2018 Elsevier B.V. All rights reserved.)