Discovery and Development of Macrolides as Anticancer Agents.

Cancer is a life-threatening destructive disease. In the past several decades, the incidence of cancer has been dramatically increased mostly due to lifestyle changes. Chemotherapy plays an important role in the treatment of cancer, but the development of resistance against chemotherapeutic agents, the side effects, and non-specific toxicity threatens the efficiency of anticancer agents. Accordingly, it is important to develop novel anticancer drugs. Beyond the classical antibacterial activity, macrolides also demonstrated potential effects against both drug-sensitive and drug-resistant cancers through modulating diverse targets and signaling pathways, so rational design of macrolides may generate valuable therapeutic interventions for the treatment of cancers. The purpose of the present review article is to outline the current developments in macrolides with an emphasis on anticancer activity, structure-activity relationships, and mechanisms of action to lay the path for the development of novel macrolide anticancer candidates.

Anticancer potential of cardiac glycosides and steroid-azole hybrids.

Steriods are well-known scaffolds that have a widespread occurrence in different compounds characterized by extensive biological properties including anticancer activity. Structural modifications on steroids always generate potential lead compounds with superior bioactivity, and creation of steroid hybrids by combining steroid with other anticancer pharmacophores in one molecule, which can exert the anticancer activity through different mechanisms, is one of the most promising strategies to enhance efficiency, overcome drug resistance and reduce side effects. Sugars and azoles, can act on diverse receptors, proteins and enzymes in cancer cells, are pharmacologically significant scaffolds in the development of novel anticancer agents. Therefore, steroid-sugar hybrids cardiac glycosides and steroid-azole hybrids are privileged scaffolds for the discovery of novel anticancer candidates. This review emphasized on the development, the structure-activity relationship and the mechanism of action of cardiac glycosides and steroid-azole hybrids with potential application for fighting against various cancers including drug-resistant forms to facilitate further rational design of novel drug candidates covering articles published between 2015 and 2020.

The Anticancer Activity of Indazole Compounds: A Mini Review.

The incidence and mortality of cancer continue to grow since the current medical treatments often fail to produce a complete and durable tumor response and ultimately give rise to therapy resistance and tumor relapse. Heterocycles with potential therapeutic values are of great pharmacological importance, and among them, indazole moiety is a privileged structure in medicinal chemistry. Indazole compounds possess potential anticancer activity, and indazole-based agents such as, axitinib, lonidamine and pazopanib have already been employed for cancer therapy, demonstrating indazole compounds as useful templates for the development of novel anticancer agents. The aim of this review is to present the main aspects of exploring anticancer properties, such as the structural modifications, the structure-activity relationship and mechanisms of action, making an effort to highlight the importance and therapeutic potential of the indazole compounds in the present anticancer agents.

Recent advances in indole dimers and hybrids with antibacterial activity against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA), one of the major and most dangerous pathogens in humans, is a causative agent of severe pandemic of mainly skin and soft tissue and occasionally fatal infections. Therefore, it is imperative to develop potent and novel anti-MRSA agents. Indole derivatives could act against diverse enzymes and receptors in bacteria, occupying a salient place in the development of novel antibacterial agents. Dimerization and hybridization are common strategies to discover new drugs, and a number of indole dimers and hybrids possess potential antibacterial activity against a panel of clinically important pathogens including MRSA. Accordingly, indole dimers and hybrids are privileged scaffolds for the discovery of novel anti-MRSA agents. This review outlines the recent development of indole dimers and hybrids with a potential activity against MRSA, covering articles published between 2010 and 2020. The structure-activity relationship and the mechanism of action are also discussed to facilitate further rational design of more effective candidates.

Efficient community detection algorithm based on higher-order structures in complex networks.

It is a challenging problem to assign communities in a complex network so that nodes in a community are tightly connected on the basis of higher-order connectivity patterns such as motifs. In this paper, we develop an efficient algorithm that detects communities based on higher-order structures. Our algorithm can also detect communities based on a signed motif, a colored motif, a weighted motif, as well as multiple motifs. We also introduce stochastic block models on the basis of higher-order structures. Then, we test our community detection algorithm on real-world networks and computer generated graphs drawn from the stochastic block models. The results of the tests indicate that our community detection algorithm is effective to identify communities on the basis of higher-order connectivity patterns.

Isatin-azole hybrids and their anticancer activities.

Isatin and azole moieties, which have the ability to form various noncovalent interactions with different therapeutic targets, are common pharmacophores in drug development. Isatin and azole derivatives possess promising in vitro and in vivo anticancer activity, and many of them, such as semaxanib, sunitinib, and carboxyamidotriazole, could be used to treat various cancers. Thus, it is conceivable that hybridization of the isatin moiety with azole may provide a valuable therapeutic intervention for the treatment of cancer. Substantial efforts have been made to develop isatin-azole hybrids as novel anticancer agents, and some of the isatin-azole hybrids exhibited considerable activity. This review emphasizes isatin-azole hybrids with potential anticancer activity, covering articles published between 2010 and 2019. The structure-activity relationships as well as the mechanisms of action are also discussed to provide insights for the rational design of more effective candidates.

Screening bioactive compounds with multi-targets from Rhodiola crenulata by a single column containing co-immobilized beta2-adrenergic receptor and voltage dependent anion channel isoform 1.

The pursuit of drugs having improved therapeutic efficacy necessitates increasing research on new assays for screening bioactive compounds with multi-targets. This work synthesized a chromatographic stationary phase containing co-immobilized beta2-adrenergic receptor (ß2-AR) and voltage dependent anion channel isoform 1 (VDAC-1) to achieve such purpose. Specific ligands of the two receptors (e.g. salbutamol, methoxyphenamine, ATP and NADH) were utilized to characterize the specificity and bioactivity of the column. Validated application of the stationary phase was performed by screening multi-target compounds of Rhodiola crenulata using high performance affinity chromatography coupled with ESI-Q-TOF-MS. By zonal elution, we identified salidroside as a bioactive compound simultaneously binding to ß2-AR and VDAC-1. The compound exhibited the binding sites of 1.0 × 10-7 and 4.0 × 10-7 M on the ß2-AR and VDAC-1. On these sites, the association constants were calculated to be 3.3 × 104 and 1.0 × 104 M-1. Molecular docking indicated that the binding of salidroside to the two receptors occurred on Ser169 and Phe255of ß2-AR, and the channel wall of VDAC-1. Taking together, we concluded that the column containing co-immobilized receptors has potential for screening bioactive compounds with multi-targets from complex matrices including traditional Chinese medicines.