Biomedical subjects

Madhuri Manpadi

Publications and source records attributed to Madhuri Manpadi.

3 recordsLinked to original sources

PubMed2006

Structural simplification of bioactive natural products with multicomponent synthesis: dihydropyridopyrazole analogues of podophyllotoxin.

A three-component condensation of 5-amino-3-methylpyrazole, tetronic acid, and various aromatic, heteroaromatic, and aliphatic aldehydes leads to the formation of dihydropyridopyrazole analogues of a cytotoxic lignan podophyllotoxin. This new heterocyclic scaffold-based library allows a drastic reduction of the structural complexity of the natural product with the retention of its potent cytotoxic properties. Similarly to podophyllotoxin, the presented analogues induce apoptosis in Jurkat cells.

Antineoplastic Agents↗

PubMed2006

Synthesis and biological evaluation of aromatic analogues of conduritol F, L-chiro-inositol, and dihydroconduritol F structurally related to the amaryllidaceae anticancer constituents.

Pancratistatin is a potent anticancer natural product, whose clinical evaluation is hampered by the limited natural abundance and the stereochemically complex structure undermining practical chemical preparation. Fifteen aromatic analogues of conduritol F, l-chiro-inositol, and dihydroconduritol F that possess four of the six pancratistatin stereocenters have been synthesized and evaluated for anticancer activity. These compounds serve as truncated pancratistatin analogues lacking the lactam ring B, but retaining the crucial C10a-C10b bond with the correct stereochemistry. The lack of activity of these compounds provides further insight into pancratistatin's minimum structural requirements for cytotoxicity, particularly the criticality of the intact phenanthridone skeleton. Significantly, these series provide rare examples of simple aromatic conduritol and inositol analogues and, therefore, this study expands the chemistry and biology of these important classes of compounds.

Amaryllidaceae Alkaloids↗

PubMed2006

Selectivity guidelines and a reductive elimination-based model for predicting the stereochemical course of conjugate addition reactions of organocuprates to gamma-alkoxy-alpha,beta-enoates.

Current models used to predict the stereochemical outcome of organocopper conjugate addition processes focus on the nucleophilic addition step as stereochemistry-determining. Recent kinetic, NMR, kinetic isotope effect, and theoretical density functional studies strongly support the proposal that stereochemical preferences in these processes are dictated by the reductive elimination step, transforming Cu(III) to Cu(I) intermediates. A new model that considers various steric and stereoelectronic factors involved in the transition state of the reductive elimination step is proposed and then used to interpret the results of systematic studies of arylcuprate conjugate addition reactions with cis and trans gamma-alkoxy-alpha,beta-enoates. The results give rise to the following selectivity guidelines for this process. To achieve high anti-addition diastereoselectivities the use of trans esters with a bulky nonalkoxy substituent at the gamma-position is recommended. While stereoelectronics disfavor syn-addition, a judicious choice of properly sized gamma-substituents may lead to the predominant formation of syn-products, especially with cis enoates. However, high syn-selectivities may be achieved by using gamma-amino-alpha,beta-enoates.

Alkenes↗