Anti-HIV principle

Fujioka T, Kashiwada Y, Kilkuskie RE, Cosentino EM, Balias LM, Jiang JB, Janzen WP, Chen IS, Lee K-H. (1994) Anti-AIDS agents, 11. betulinic acid and platanic acid as anti-HIV principles from syzigium claviflorum, and the anti-HIV activity of structurally related triterpenoids. J Nat Prod 57 243-247. 

Lee, T. T. Kashiwada, Y. Huang, L. Snider, J. Cosentino, M. Lee. K. H. Suksdorfin an anti-HIV principle from Lomatium suksdorfii, its structure-activity correlation with related coumarins, and synergistic effects with anti-AIDS nucleosides. Bioorg. Med. Chem., 1994, 2 1051-1056. 

DF Chen, SX Zhang, K Chen, BN Zhou, P Wang, LM Cosentino, KH Lee. Two new lignans, interiotherins A and B, as anti-HIV principles from Kadsura interior. J Nat Prod 59 1066-1068, 1996. 

Konoshima, T. Yasuda, I. Kashiwada, Y. Corentino, C.M. Lee, K.H. Anti-AIDS Agents, 21. Triterpenoid Saponins as Anti-HIV Principles from Fruits of Gleditsia japonica and Gymnocladus chinensis and A Structure Activity Correlation. J. Nat. Prod. 1995, 58, 1372-1375. 

Fujioka, T. Kashiwada, Y. Kilkuskie, R.E. Cosentino, L.M. Balias, L.M. Jiang, J.B. Janzen, W.P. Chen, I.S. Lee, K.-H. Anti-AIDS Agenta, 11. Betulinic Acid and Platanic Acid as Anti-HIV Principles from Syzigum claviflorum and The Anti-HIV Activity of Structurally Related Triterpenoids. J. Nat. Prod. 1994, 57, 243-247. 

In the course of the search for novel potent anti-AIDS agents, the ethanolic extract of the roots of T. wilfordii was found to show significant anti-HIV activity. Bioassay-directed fractionation of the active extract has led to the isolation and characterization of a new anti-HIV principle, a kaurane-type diterpene lactone, tripterifordin (90), Fig (27). This compound inhibited HIV replication in H9 lymphoc e cells with an EC50 of 1 pg/ml (6 (M) but it did not inhibit uninfected H9 cell growth at 15 xM [180]. From the same species a new kaurene type diterpene, neotripterifordin (91) was also isolated, which showed potent anti-HIV replication activity in H9 lymphocyte cells with an EC50 of 25 nM and a... 

Ishida, J. Wang, H. Oyama, M. Cosentino, M. L. Hu, C. Lee, K. Anti-AIDS agents. 46. Anti-HIV activity of harman, an anti-HIV principle from Symplocos setchuensis, and its derivatives. J. Nat. Prod. 2001, 64, 958-960. 

Chen K, Shi Q, Fujioka T et al (1995) Anti-AIDs agents - XIX. Neotripterifordin, a novel anti-HIV principle from Tripterygium wilfordii isolation and structural elucidation. Bioorg Med Chem 3 1345-1348... 

Numerous important bioactive compounds have been, and continue to be, isolated worldwide from natural sources. These compounds include both primary and secondary metabolites isolated mainly from plants, as well as from the animal and mineral kingdoms. The recent development of new bioassay methods has facilitated progress in the BDFI (bioactivity-directed fractionation and isolation) of many useful bioactive compounds from natural sources (1). These active principles could be developed or additionally modified to enhance the biologic profiles as clinical trials candidates. Many natural pure compounds have become medicines, dietary supplements, and other useful commercial products. This article summarizes research on many different useful compounds isolated or developed from plants with an emphasis on those discovered recently by the laboratories of the authors as antitumor and anti-HIV clinical trial candidates. 

Acetate is also a precursor of several groups of alkaloids in the form of a polyketide chain that interacts with an unknown nitrogen source (as in the terpene alkaloids). Examples of acetate-derived alkaloids are coniine—the toxic principle of Conium maculatum, pinidine—from several Pinus species, and the naphthy-lisoquinoline alkaloids (e.g., ancistrocladine)—showing antimalarial and anti-HIV activity. The latter alkaloids are apparently derived from the oxidative coupling of two pentaketide units. Huperzine A, currently in clinical trials for the treatment of Alzheimer s disease and isolated from the club moss (Serrata huperzia), is derived from a polyacetate precursor (Fig. 46). 

The sites at which anti-HIV drugs may. in principle, act, are dealt with in detail under a main heading (see ANTIVIRAL agents). In summary, currently, of the drugs actually in use, a number are reverse transcriptase (enzyme) inhibitors (RTIs). Examples of nucleoside RTIs include zidovudine, didanosine and zalcitabine. Some non-nucleoside RTIs include foscarnet sodium, nevirapine, carbovir and TIBO analogues (some of these are at trial stage only). 

Passive antibody vaccines have been prepared up to now from human blood serum. Consequently, there has been no need for cultivation methods beyond vaccination and conventional harvest of antibody-containing blood from donors. Due to safety concerns over using human blood, passive vaccines will likely be monoclonal antibodies or cocktails thereof prepared in vitro by the cultivation of hybridoma or myeloma cell lines. This approach is under investigation for anti-HIV-1 antibodies [Emini et al., 1992]. Cultivation of these cell lines involves the same principles of animal cell cultivation as described above, with the exception that hybridomas can be less fastidious in nutritional requirements, and they do not require surface attachment for growth. These features will allow for defined serum-free media and simpler cultivation vessels and procedures. 

Worth also to remark that in the present uracils derivatives anti-HIV analysis, the four-descriptors dependency is not necessary in variational construct of Eq. (3.171) since not need in assessing the structural/reactivity parameters hierarchy in minimum variational path principle of Eq. (3.171) through being absorbed in the rest of correlations by means of the transitivity chain rule (Putz Duda , 2013a, b) ... 

Equation (3.283) may be represented by the orbital based scheme of chemical reactivity driving biological (anti-HIV) activity as provided in Figure 3.32 it is explained in Ihe light of chemical reactivity principles, see the Section 3.2.9 and the Voliune III of the present five-volume work (Putz, 2016c), within the time-space framework fixed by the chemical reactivity- biological activity interaction ... 

Putz, M. V., Duda , N. A. (2013a). Variational principles for mechanistic quantitative structure-activity relationship (QSAR) studies application on uracil derivatives anti-HIV action. Struct. Chem. 24(6), 1873-1893 (DOI 10.1007/sll224-013-0249-6). 

Gotte M. Inhibition of HIV-1 reverse transcription basic principles of drug action and resistance. Expert Rev Anti Infect Ther. 2004 2 707-716. 

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