Synthesis and Structure−Activity Relationships of New Benzodioxinic Lactones as Potential Anticancer Drugs

Abstract

A set of disubstituted tetracyclic lactones has been synthesized and tested for potential antitumor activity. Several of them possess a noticeable cytotoxicity against L1210 and HT-29 colon cells in vitro. Relationships between chain nature and biological properties were sought. Lactones with a pentyl or hexyl substituent at C-11 are the most active ones. The introduction of a functional group at the side chain of C-11 modified the potency; carboxylic acid and primary amine decreased the cytotoxicity, whereas a cyano group increased the activity. An extensive structure-activity relationship study of these derivatives, including carbon homologues and bioisosteres has been performed. The synthesis and cytotoxicity of these compounds are discussed. Two lactones are recognized as potential lead compounds.

1,4-Diazabicyclo[2.2.2]octane (DABCO) as a useful catalyst in organic synthesis

“…The cyano group is a prominent functional motif found in several bioactive molecules and plays a significant role by hydrogen bonding to certain biological receptors [58]. In this method, a simple conversion of aldoximes to nitriles using DABCO-POCl3 as an inexpensive and useful reagent was demonstrated (Scheme 31) [59].…”

Synthesis of Some Novel D‐Glucuronic Acid Acetylated Derivatives as Potential Anti‐Tumor Agents

“…The formation of 1 was confirmed by 1 H-NMR spectroscopy. In particular, the acetoxy methyl signal that appeared at relatively low field (2.28 ppm) indicates the existence of the COOCOCH 3 group, in addition to the higher field signals observed at 2.13 (3H), 2.05 (6H) and 2.04 ppm (3H) which corresponds to the four O-acetyl groups.…”

“…1). The synthesis of new compounds and testing their biological and pharmacological activities are the major goals of drug development projects [1]. Sialic acids are involved in a range of biological processes including cell-cell, cell-microbe interactions [2][3][4], masking effects for cell surface antigen [5,6], differentiation of cells [7][8][9], and neoplastic transformation [10][11][12].…”

Induction of apoptosis by cyclobutanones and derived polycyclic γ-lactones: a preliminary analysis of antiproliferative activity

“…[1][2][3][4][5][6][7][8][9][10] Molecules possessing four-and five-membered cyclic ketone moieties display broad pharmacological profiles which include antitumor, fungicidal, anthelmintic, antiviral, anti-inflammatory, anti-allergenic, antimicrobial and anti-HIV. [1][2][3][4][5][6][7][8][9][10] Molecules possessing four-and five-membered cyclic ketone moieties display broad pharmacological profiles which include antitumor, fungicidal, anthelmintic, antiviral, anti-inflammatory, anti-allergenic, antimicrobial and anti-HIV.…”