Results of the last 15-20 years on the isolation, synthesis, chemical modification, and biological activity of natural tricyclic quinazolines and their synthetic analogs were reviewed.

This study investigates a proposed design of a peptide sequence that is based on a bioactive conformation of statins that act as the competitive inhibitors of HMG-CoA for HMGR. To bridge these heterogeneous organic compounds, a conformational aspect relating to an analysis of the flexibility of the peptide molecules and their occupied volumes was applied to the peptide design. The design criterion was formulated in terms of a proximity parameter (Pr), reflecting the probability of an active peptide conformation to approximate the statin. Through a structure-functional analysis of previously synthesized peptides and statin molecules, nine peptides were selected for the peptide library. Comparing the calculated proximity parameters, four peptides (IAVE, YAVE, IVAE, and YVAE) from the library were selected and synthesized. In vitro assays elucidated the inhibition properties for HMGR that are exhibited by these peptides. Among all peptides, YVAE showed the highest ability to inhibit HMGR. A kinetic analysis revealed that this peptide is a competitive inhibitor of HMG-CoA with an equilibrium constant of inhibitor binding (K(i)) of 15.2 +/- 1.4 microM. The calculated coefficient correlation (R) between log (IC(50)) and the inverse value of proximity parameter (1/Pr) was found to be 0.99, indicating a high degree of correlation and efficacy of the given approach in the peptide sequence design.

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Polyprenols and triterpenoids from leaves of Alcea nudiflora were studied for the first time. It was shown that the principal components of the unsaponified fraction were polyprenols, sterols, a phytol, and tocopherols. The composition of the polyprenols from Alcea nudiflora was established. Minor components of polyprenols with chain lengths 8, 9, and 14 isoprene units were observed for the first time in plants of the genus Alcea. A total of 28 terpene components of the unsaponified fraction, 26 of which were not previously observed in this species, were determined by GC-MS.Plants of the family Malvaceae are exceptional among leafy plants because of their high content of polyprenols (PPs), which are chemotaxonomic markers [1][2][3][4][5][6]. Such plants also have a characteristically high content of cyclopropane acids, which are practically not observed in plants of other families [7].Alcea nudiflora belongs to this family, is widely distributed, and is common in the plant cover of the whole Tian-Shan (Chatkal, Kuramin, Ugam, Pskom, etc. ranges) and Pamir-Alai (Alai, Turkestan, Nuratau, Zarafshan, etc. ranges) [8-10]. However, neutral triterpenoids and bioactive PPs from this plant are insufficiently studied [11].Various qualitative and quantitative analytical methods for PPs and dolichols from plant material have been reported. However, each of them has certain shortcomings. Thus, comparison of HPLC analyses of an extract and a chromatographic standard concentrate of PPs does not consider seasonal cycles of the component ratio in plant material according to vegetation periods. Furthermore, PPs and dolichols in certain plant species are present as esters of aliphatic acids that are unsuitable for HPLC analysis [12,13]. HPLC with refractive-index detection also has shortcomings. Normalization to the total peak area in the chromatogram does not consider differences in the extinction or refraction.PMR analysis of polyisoprenoid concentrates also has several shortcomings. A PMR spectrum of a PP sample is a superposition of resonances of similar structural fragments. The regular structure of the PPs produces total resonances that are stronger than those of impurities. This leads to a substantial overestimation of the quantitative characteristics of the studied PP fraction. Solanesol can be cited as an example [14].Use of densitometry of thin-layer chromatograms compared with a standard [15] also usually causes substantial overestimation of quantitative results because accompanying mono-, sesqui-, and diterpene alcohols overlap the spot for the PP fraction. Thus, borneol, cis-abienol, isoabienol, dehydroabietinol, and other alcohols that enhanced the intensity of the PP spot were present as impurities in the total fraction during a study of PPs from conifers [16,17]. Bisabolol was isolated from essential oil of cotton buds [18]. The chromatographic mobility of total extracted compounds depends on the chain length of the PPs in them and their form (as alcohols or esters). Therefore it is practically impossible to choose...

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