Anti-HIV activity of natural triterpenoids and hemisynthetic derivatives 2004–2009

Abstract

The continued advance of HIV-AIDS makes the development of relatively inexpensive, freely accessible, and mechanistically more diverse antiviral therapies an urgent need. Natural products are, directly or indirectly, an important potential source of compounds meeting these conditions. A review of the recent literature indicates that some hemisynthetic triterpenoid derivatives, particularly belonging to the lupane, oleanane and ursane series, may be nearing a stage where they can be used to complement existing therapeutic approaches. On the other hand, although some natural derivatives of tetracyclic terpenoid families have revealed many novel structures and some promise as anti-HIV substances, their chemical modification to improve their potency and selectivity remains practically untouched. While ongoing work with the more 'classical' pentacyclic triterpenoids will continue to be a fertile field for HIV-AIDS drug discovery, the other structural groups offer unprecedented opportunities for the development of additional substances with useful properties and for the discovery of novel targets for antiviral therapy.

Molecular Rearrangements of Highly Functionalized Terpenes. An Unique Reactivity of Bicyclic Framework and Polienic Chain Inhibition under Superacidic Treatment

“…Synthesis of fragment B has been achieved starting from commercially available manool (5). It was transformed into new diterpenic phenylsulfone 6 in a two-step sequence, according to the reported method [12].…”

“…Reviews related to biological activities of triterpenes appear regularly and are focused on their anti-infl ammatory [4], antitumor [5], anti-HIV [6,7] and insecticidal [8] activities, and also their use in treatment of metabolic and vascular diseases [9].…”

Simple structural modifications confer cytotoxicity to allobetulin

“…m = 3473w, 3082w, 2949s, 2862s, 1745s, 1636w, 1460m, 1419w, 1386s, 1360m, 1296m, 1253w, 1184m, 1154s, 1068w Butyl (18a,19b) 19,28-epoxy-3,4-seco-18-olean-4(23)-ene-carboxylate (15) Following the procedure given for the synthesis of 11, from 10 (150 mg, 0.33 mmol), potassium carbonate (0.80 g, 0.58 mmol), DMF (15 mL) and n-butylbromide (0.04 mL, 0. (5)), 2.24 (dd, J = 12.3, 2.0 Hz, 1H, CH (9)), 1.71-1.59 (m, 1H, CH a (15)), 1.58-1.44 (m, 7H, CH a (6) + CH a (11) + CH a (7) + CH (18) + CH (13) + CH a (12) + CH a (22) (34)), 4.02 (t, J = 6.7 Hz, 2H, CH 2 (31)), 3.88 (dt, J = 10.8, 6.5 Hz, 1H, CH b (34)), 3.76 (d, J = 7.6 Hz, 1H, CH a (28)), 3.52 (s, 1H, CH (19)), 3.43 (d, J = 7.7 Hz, 1H, CH b (28)), 2.51-2.43 (m, 2H, CH 2 (1)), 2.43-2.40 (m, 1H, CH (5)), 2.27-2.20 (m, 1H, CH (9)), 1.72-1.58 (m, 5H, CH 2 (32) + CH 2 (35) + CH a (15)), 1.59-1.44 (m, 7H, CH a (11) + CH a (6) + CH a (7) + CH (18) + CH a (12) + CH a (22) + CH (13)), 1.43-1.33 (m, 4H, CH a (21) + CH b (7) + CH b (6) + CH a (16)), 1.34-1.17 (m, 4H, CH b (22) + CH b (16) + CH b (7) + CH b (11)), 1.27 (s, 3H, CH 3 (24)), 1.26 (s, 3H, CH 3 (23)), 1.15-1.06 (m, 1H, CH b (12)), 1.00-0.84 (m, 7H, CH b (15) + CH 3 (33) + CH 3 (36)), 0.96 (s, 3H, CH 3 (26)), 0.94 (s, 3H, CH 3 (25)), 0.92 (s, 3H, CH 3 (30)), 0.91 (s, 3H, CH 3 (27)), 0.78 (s, 3H, CH 3 (29)) ppm; 13 Diallyl (18a,19b) 19,28-epoxy-2,3-seco-18-oleanan-2,3-dicarboxylate (23) Following the procedure given for the synthesis of 11, from 19 (200 mg, 0.41 mmol) potassium carbonate (0.22 g, 1.59 mmol), DMF (15 mL) and allyl iodide (0.09 mL, 0.95 mmol) followed by chromatography (SiO 2 , hexane/ethyl acetate, 9:1) 23 (150 mg, 64%) was obtained as a colorless solid; R f = 0.64 (hexane/ethyl acetate, 8 2927s, 2862s, 1720s, 1648m, 1451s, 1374s, 1338m, 1284s, 1256s, 1235s, 1208s, 1133s, 1059m, 1038s, 1008s cm À1 ; 1 …”

“…1 Natural triterpenoids 2 have been used in traditional medicine for their anticancer, antiviral/virostatic, anti-inflammatory and hepatoprotective activity. [3][4][5][6][7][8][9][10][11] These triterpenes are important for the survival of the plant, and they form a wide family of compounds. They are biosynthesized by numerous higher plants and some higher fungi from 2,3-epoxy-squalene by a cyclization reaction; by this way, most abundant betulin ( Fig.…”

Synthesis and anticancer activity of aminopropoxytriterpenoids

“…The derivatives of triterpenoids have been one of the most interesting areas of research in the past years due to their broad range of biological and medicinal properties (Cassels and Asencio, 2011;Csuk et al, 2013b;Dzubak et al, 2006;Kuo et al, 2009;Laszczyk, 2009;Sheng and Sun 2010;Salvador et al, 2012;Shanmugam et al, 2012).…”