Recent Advances in the Chemistry and Therapeutic Evaluation of Naturally Occurring and Synthetic Withanolides

Abstract

Natural products are a major source of biologically active compounds that make promising lead molecules for developing efficacious drug-like molecules. Natural withanolides are found in many flora and fauna, including plants, algae, and corals, that traditionally have shown multiple health benefits and are known for their anti-cancer, anti-inflammatory, anti-bacterial, anti-leishmaniasis, and many other medicinal properties. Structures of these withanolides possess a few reactive sites that can be exploited to design and synthesize more potent and safe analogs. In this review, we discuss the literature evidence related to the medicinal implications, particularly anticancer properties of natural withanolides and their synthetic analogs, and provide perspectives on the translational potential of these promising compounds.

Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal

“…The bioactive compound withaferin A is a steroidal lactone primarily extracted from W. somnifera , first isolated by Israeli chemists, Asher Lavie and David Yarden, in 1962 from the leaves of the plant. The inhibitory properties of the withaferin A molecule are due to the occurrence of an unsaturated lactone in a side chain; allylic 1° alcohol is attached at position 25 and the highly oxygenated rings A and B are attached to the other side of the compound [ 32 , 33 , 34 , 35 , 36 ]. Cytotoxicity is achieved by the presence of α,β-unsaturated carbonyl moiety of the withaferin A structure of thiol adducts [ 37 ].…”

Novel pyrazole and imidazolone compounds: synthesis, X-ray crystal structure with theoretical investigation of new pyrazole and imidazolone compounds anticipated insecticide’s activities against targeting Plodia interpunctella and nilaparvata lugens

“…The multifaceted activities of oxiranes and their derivatives in terms of anti-microbial, anti-cancer, and anti-tumor have been investigated by bio-chemists and chemists. [1][2][3][4][5] For synthesis of oxiranes from chalcones and alkenes, numerous reagents and catalysts have been utilized. 6 These epoxides are exible chemicals that can easily undergo stereospecic ring-opening reactions to generate multifunctional molecules.…”

ADMET-informatics, Pharmacokinetics, Drug-likeness and Medicinal Chemistry of Bioactive Compounds of Physalis minima Ethanolic Leaf Extract (PMELE) as a Potential Source of Natural Lead Molecules for Next Generation Drug Design, Development and Therapies

“…Alternatively, development of novel and sensitive techniques to detect biologically active PBNPs, advanced techniques to isolate, purify and structurally characterize PBNPs, and advances to meet out demand-supply aspects of PBNPs have prompted interest in development and promotion of herbal drugs. In recent years, both combinatorial chemistry and highthroughput screening platforms have significantly increased the number of compounds for which early data on absorption, distribution, metabolism, excretion (ADME) and toxicity (T) are not available, which has led to the development of a variety of medium and high-throughput in vitro ADMET screens for drug development and design with deeper dimension with high degree of precision taking into account cost economics and time [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] .…”