1. Medial Arterial Calcification: JACC State-of-the-Art Review
Peter Lanzer, et al. J Am Coll Cardiol. 2021 Sep 14;78(11):1145-1165. doi: 10.1016/j.jacc.2021.06.049.
Medial arterial calcification (MAC) is a chronic systemic vascular disorder distinct from atherosclerosis that is frequently but not always associated with diabetes mellitus, chronic kidney disease, and aging. MAC is also a part of more complex phenotypes in numerous less common diseases. The hallmarks of MAC include disseminated and progressive precipitation of calcium phosphate within the medial layer, a prolonged and clinically silent course, and compromise of hemodynamics associated with chronic limb-threatening ischemia. MAC increases the risk of complications during vascular interventions and mitigates their outcomes. With the exception of rare monogenetic defects affecting adenosine triphosphate metabolism, MAC pathogenesis remains unknown, and causal therapy is not available. Implementation of genetics and omics-based approaches in research recognizing the critical importance of calcium phosphate thermodynamics holds promise to unravel MAC molecular pathogenesis and to provide guidance for therapy. The current state of knowledge concerning MAC is reviewed, and future perspectives are outlined.
2. Potent immunosuppressants, 2-alkyl-2-aminopropane-1,3-diols
T Fujita, R Hirose, M Yoneta, S Sasaki, K Inoue, M Kiuchi, S Hirase, K Chiba, H Sakamoto, M Arita J Med Chem. 1996 Oct 25;39(22):4451-9. doi: 10.1021/jm960391l.
Several immunosuppressants, ISP-I [(2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoeicos++ +-6-enoic acid, myriocin = thermozymocidin] and mycestericins A-G, were isolated from culture broths of Isaria sinclairii and Mycelia sterilia, respectively. In order to investigate structure-activity relationships, extensive modifications of ISP-I were conducted, and it was established that the fundamental structure possessing the immunosuppressive activity is a symmetrical 2-alkyl-2-aminopropane-1,3-diol. The tetradecyl, pentadecyl, and hexadecyl derivatives prolonged rat skin allograft survival in the combination of LEW donor and F344 recipient and were more effective than cyclosporin A. Among them, 2-amino-2-tetradecylpropane-1,3-diol hydrochloride, ISP-I-55, showed the lowest toxicity. ISP-I-55 is a promising lead compound for the development of effective immunosuppressants for organ transplantations and for the treatment of autoimmune diseases.
3. (2 R,3 R)-1,4-Dioxa-spiro-[4.4]nonane-2,3-di-carb-oxy-lic and (2 R,3 R)-1,4-dioxa-spiro-[4.5]decane-2,3-di-carb-oxy-lic acids
Mikhail E Minyaev, Dmitrii M Roitershtein, Alexey A Vinogradov, Ivan V Ananyev, Ilya E Nifant'ev Acta Crystallogr E Crystallogr Commun. 2018 Jul 6;74(Pt 8):1058-1062. doi: 10.1107/S2056989018009593. eCollection 2018 Aug 1.
The title compounds, C9H12O6 and C10H14O6, were formed by careful hydrolysis of the corresponding diethyl esters. Their single crystals were grown from an ethyl acetate/hexane mixture. Crystals of both compounds have monoclinic (P21) symmetry with a single mol-ecule in the asymmetric unit. Both crystal structures are very similar and display four -CO-OH⋯O=C(OH)- hydrogen bonds, forming a two-dimensional double-layered framework.
