Diosgenone Synthesis, Anti-Malarial Activity and QSAR of Analogues of This Natural Product

Abstract

Solanum nudum Dunal steroids have been reported as being antimalarial compounds; however, their concentration in plants is low, meaning that the species could be threatened by over-harvesting for this purpose. Swern oxidation was used for hemisynthesis of diosgenone (one of the most active steroidal sapogenin diosgenin compounds). Eighteen structural analogues were prepared; three of them were found to be more active than diosgenone (IC 50 27.9 μM vs. 10.1 μM, 2.9 μM and 11.3 μM). The presence of a 4-en-3-one grouping in the A-ring of the compounds seems to be indispensable for antiplasmodial activity; progesterone (having the same functional group in the steroid A-ring) has also displayed antiplasmodial activity. Quantitative correlations between molecular structure and bioactivity were thus explored in diosgenone and several derivatives using well-established 3D-QSAR techniques. The models showed that combining electrostatic (70%) and steric (30%) fields can explain most variance regarding OPEN ACCESSMolecules 2013, 18 3357 compound activity. Malarial parasitemia in mice became reduced by oral administration of two diosgenone derivatives.

N‐Cinnamoylation of Antimalarial Classics: Effects of Using Acyl Groups Other than Cinnamoyl toward Dual‐Stage Antimalarials

“…The toxicity of compounds 9 and 10 against HepG2 cells was determined (Table 1) as previously described 10. All compounds except 9 f (CC 50 =125 μ M ) were more cytotoxic than CQ (CC 50 =97.2 μ M 16), displaying CC 50 values below 40 μ M . CQ analogues 9 (9.20 μ M ≤CC 50 ≤125 μ M ) were less cytotoxic than QC analogues 10 , the latter being more cytotoxic (0.76 μ M ≤CC 50 ≤3.65 μ M ) than the parent drug QC (CC 50 =7.40 μ M ).…”

Structural Diversity of Diosgenin Hydrates: Effect of Initial Concentration, Water Volume Fraction, and Solvent on Crystallization

“…Diosgenin [or (22R,25R)-spirost-en-3β-ol) as a steroid sapogenin available from natural sources is widely used for the commercial synthesis of steroid drugs like cortisone and progesterone . Recently, some significant biological activities of diosgenin, such as anticancer, , antiviral, , antihyperlipidemic, , and antimalarial , activities, have been reported. The molecular structure of diosgenin is shown in Scheme .…”

Synthesis, Characterization, and Solid State Dynamic Studies of a Hydrogen Bond-Hindered Steroidal Molecular Rotor with a Flexible Axis

“…The alkynone 4 was obtained through a three-step sequence that included (i) Oppenauer oxidation of diosgenin (1) , (ii) H 2 O 2 /NaOH epoxidation of the α,β-unsaturated ketone 2 to produce a 1/3.02 mixture of the known epimeric epoxides (3a) and (3b ) that resisted all attempts at separation and (iii) Eschenmoser-Tanabe fragmentation of the mixture of the epoxides 3α and 3β . Sonogashira coupling of 4 with 1,4-diiodobenzene or 1,4-diiodobenzene-D 4 afforded the dimers 5a or 5b , respectively (Scheme ).…”

“…The solid was filtered, washed with water, and dried in the filter. Crystallization from hexane ethyl acetate afforded 6.46 g (75.4%) of a 1/3.02 mixture of the known epimeric epoxides (3a) and (3b ) that resisted all attempts at separation and was used in the next step without further purification or separation. DR was calculated by relative integration of the signals of H-4 in each epimer).…”