Calixarenes and their Relevance in Anticancer Drug Development.

Calixarenes have always captured the attention of several researchers. They have the ability to entrap multiple molecules and form inclusion complexes with drugs due to their unique structure. Due to this property, they are being widely used in the development of several classes of drugs, most notably anticancer drugs. This review attempted to summarize the potential applications of calixarenes and its derivatives in the development of anticancer drugs, with a focus on the delivery of drug classes such as DNA intercalators, taxanes, DNA alkylators, and topoisomerase inhibitors. Calixarene-based macromolecular chemistry could therefore have a high potential for overcoming the toxicity of cancer chemotherapy and achieving targeted drug delivery.

NF-κB Regulation by Gut Microbiota Decides Homeostasis or Disease Outcome During Ageing.

Human beings and their indigenous microbial communities have coexisted for centuries, which led to the development of co-evolutionary mechanisms of communication and cooperation. Such communication machineries are governed by sophisticated multi-step feedback loops, which typically begin with the recognition of microbes by pattern recognition receptors (PRRs), followed by a host transcriptional response leading to the release of effector molecules. Our gastrointestinal tract being the main platform for this interaction, a variety of host intestinal cells tightly regulate these loops to establish tolerance towards the microbial communities of the gut and maintain homeostasis. The transcription factor, nuclear factor kappa B (NF-κB) is an integral component of such a communication apparatus, which plays a critical role in determining the state of homeostasis or inflammation associated with dysbiosis in the host. Here we outline the crucial role of NF-κB in host response to microbial cues in the context of ageing and associated diseases.

Bioisosterism in Drug Discovery and Development - An Overview.

Bioisosterism is a unique approach used by medicinal chemists for the reasonable modification of lead compounds into safer, more clinically effective, economical, and therapeutically attractive drugs. It is one of the most crucial lead modification tools, widely applied in the field of rational drug design to amplify the desired activity and eliminate undesirable properties, thus facilitating the optimization of pharmacokinetic profile and achievement of target selectivity. This review demonstrates the importance of bioisosterism in the process of drug discovery and development and highlights its relevance in the molecular evolution of many classes of drugs such as antibacterial sulfonamides, anticancer drugs, antivirals, antifungals, anthelmintics, local anesthetics, barbiturates, antidepressants, antihistamines, proton pump inhibitors and work carried out by our team of researchers. The role of bioisosterism as a strategy to achieve inhibition of enzymes such as thymidylate synthase, DNA polymerase, reverse transcriptase and several others has also been pointed out. There are no limits to the classes of drugs where bioisosterism has been successfully applied.