Current Protein and Peptide Science - Volume 24, Issue 10, 2023

Background: The cancer is still a major cause of death worldwide. Among different targets to design anticancer agents, caspase-3 is an important target as its cleavage and activation lead to apoptosis and finally, cancer cell death. Apart from some naturally occurring molecules, many small molecules have been reported as caspase-3 activators.Objectives: In view of the above, the objective has been to review the published work on small molecules reported as caspase-3 activators and their anticancer activity to get some novel lead molecules for designing novel molecules of improved cancer therapeutic.Methods: Literature search has been carried out using different search engines like google, Elsevier, Science direct, RSC, etc. for the publications of small molecules as caspase-3 activators inducing apoptosis in cancer cells.Results: In this review, the small molecules showing caspase-3 cleavage and activation have been discussed under different broad chemical classes so as to provide some insight into the structural features responsible for caspase-3 activation leading to anticancer activity. The review also encompasses the established drugs, novel organometallics showing caspase-3 activation and anticancer activity.Conclusion: A large number of small molecules including some established drugs and organometallics have shown cleavage and activation of caspase-3 leading to apoptosis and anticancer activity. Many reported potent molecules of different chemical classes may be useful as lead molecules for optimization of anticancer activity as well as they may provide an insight of structural features which may be useful in designing novel caspase-3 activators as anticancer agents for drug development.

Cyanobacteria have been recognized as a rich source of bioactive metabolites with potential biotechnological applications in the pharmacological industry. The chemically diverse natural compounds or their analogues cause cytotoxicity. They may kill various cancer cells by inducing apoptosis or changing the activation of cell signaling, particularly involving the protein kinase-C family of enzymes, mitochondrial dysfunctions, and oxidative damage. B cell lymphoma 2 (Bcl-2) is an essential component of apoptosis and is an antiapoptotic molecule. The key apoptotic regulators associated with cancer are members of the Bcl-2 protein family, the key member of which is Bcl-2. The Bcl-2 protein is a promising target for the emergence of new anti-tumor therapies because of its critical role in controlling apoptosis. This review explores the significance of Bcl-2 in the onset of cancer; it may be used as a target for developing high-quality drug therapies to treat various tumors. In addition, a number of computational techniques were used to identify novel hit compounds that may act as inhibitors of the apoptotic protein Bcl-2, including virtual screening, toxicity prediction, and drug-likeness analysis. Twenty-three compounds were assessed as potential hits against Bcl-2, and these compounds were subjected to ADMET property prediction. Dendroamide A and Welwitindolinone A appear to be the most stable and effective drugs against Bcl-2 out of all those evaluated. This article gives an overview of the bioactive compounds produced by cyanobacteria that have anticancer properties and may be exploited to create novel anticancer medications in the future.

Nowadays, discovering an effective and safe anticancer medication is one of the major challenges. Premature death due to the unidirectional toxicity of conventional therapy is common in cancer patients with poor health status. Plants have been used as medicine since prehistoric times, and extensive research on the anticancer properties of various bioactive phytomolecules is ongoing. Pentacyclic triterpenoids are secondary metabolites of plants with well-known cytotoxic and chemopreventive properties established in numerous cancer research studies. The lupane, oleanane, and ursane groups of these triterpenoids have been well-studied in recent decades for their potential antitumor activity. This review delves into the molecular machinery governing plant-derived triterpenes' anticancer efficacy. The highlighted mechanisms are antiproliferative activity, induction of apoptosis through regulation of BCL-2 and BH3 family proteins, modulation of the inflammatory pathway, interference with cell invagination and inhibition of metastasis. Lack of solubility in mostly used biological solvents is the major barrier to the therapeutic progress of these triterpenoids. This review also highlights some probable ways to mitigate this issue with the help of nanotechnology and the modification of their physical forms.

Cancer diseases account for about 15% of deaths globally right now, and the percentage may increase in the future. There are more than 100 types of cancer, and each of them is distinct in its origin, microenvironment, growth, metastasis, and signalling pathways. Cancer stem cells are the specialised cells that make cancer more aggressive and difficult to treat. Moreover, cancer aetiology may exist at the genomic, proteomic, or habitat level in any combination. Hence, a unanimous treatment protocol for the different cancers is an uphill task at the present juncture. In this context, this review aims to provide a comprehensive reappraisal concisely of anti-apoptotic proteins, which are shown to be overexpressed in most cancers, if not all, and to forthrightly rationalise the apoptotic proteins as potential biomarkers and druggable targets of the cancers by effectively killing cancer stem cells.

Apoptosis, a natural process of programmed cell death, is a promising therapeutic target as the disruption of apoptosis evolves in many diseases including cancer. Several pieces of evidence indicate that errors in apoptotic pathways result in the imbalance between cell proliferation and death, allowing cells with genetic abnormalities to survive. The intrinsic and extrinsic pathways of apoptosis utilize different caspases to execute the event of cell death through the cleavage of hundreds of proteins. Proteins from the Bcl-2 family, a pivotal component of the mitochondrial apoptosis pathway, activate the death signal either directly or indirectly involving mitochondrial translocation of Bax/Bak, which are recognized critical elements in defective apoptosis. The majority of chemotherapeutic drugs destroy cancer cells by activating the apoptotic machinery via Bcl-2/Bax-dependent process and failure of which leads to an intrinsic chemoresistance. Recent insights into the dynamic action of pro-survival Bcl-2 proteins in cancer pathogenesis and resistance has set the stage for the development of small molecules as Bcl-2 antagonist and modulators of apoptosis. The BH3-only proteins are vital inducers of the mitochondrial apoptosis mechanism that operate either by assuming the functional activity of the proapoptotic Bcl-2 family members or by impeding the antiapoptotic Bcl-2 proteins. Based on the structural interaction studies between the proapoptotic and anti-apoptotic proteins, several synthetic peptides have been designed to functionally mimic the BH3 domain, targeting directly the pro-survival Bcl-2 proteins. The "BH3-peptide mimetics" a novel class of Bcl-2 protein antagonists essentially play an important role in the treatment of malignancies as they are predicted to persuade non-receptor mediated programmed cell death. This review summarizes the most promising BH3-peptide mimetic compounds that function as selective antagonists of Bcl-2 proteins and would be effective in treating various cancers.

Introduction: The proteins of the Bin/Amphiphysin/Rvs167 (BAR) domain superfamily are believed to induce membrane curvature. PICK1 is a distinctive protein that consists of both a BAR and a PDZ domain, and it has been associated with numerous diseases. It is known to facilitate membrane curvature during receptor-mediated endocytosis. In addition to understanding how the BAR domain facilitates membrane curvature, it's particularly interesting to unravel the hidden links between the structural and mechanical properties of the PICK1 BAR domain.Methods: This paper employs steered molecular dynamics (SMD) to investigate the mechanical properties associated with structural changes in the PICK1 BAR domains.Results: Our findings suggest that not only do helix kinks assist in generating curvature of BAR domains, but they may also provide the additional flexibility required to initiate the binding between BAR domains and the membrane.Conclusion: We have observed a complex interaction network within the BAR monomer and at the binding interface of the two BAR monomers. This network is crucial for maintaining the mechanical properties of the BAR dimer. Owing to this interaction network, the PICK1 BAR dimer exhibits different responses to external forces applied in opposite directions.

The authors declare after the publication of the article titled 128;β-Barrel Membrane Bacterial Proteins: Structure, Function, Assembly and Interaction with Lipids'', published in Current Protein and Peptide Science, 2007, 8, 63-82 [1], that a reference by Koebnik was inadvertently omitted. The missing reference has now been included as:Original:All donors and acceptors are saturated intrasegmentally in -helices or intersegmentally in -barrels by the formation of hydrogen bonds between adjacent -strands [1].[1] Rosenbusch, J.P. (1988) Zentralbl. Bakteriol. 17, 259-266.Corrected: All donors and acceptors are saturated intrasegmentally in α-helices or intersegmentally in β-barrels by the formation of hydrogen bonds between adjacent β-strands [1a, 1b].[1a] Rosenbusch, J.P. (1988) Zentralbl. Bakteriol. 17, 259-266.[1b] Koebnik, R.; Locher, K.P.; Gelder, P.V. Structure and function of bacterial outer membrane proteins: barrels in a nutshell. Mol. Biol., 2000, 37(2), 239-53.The original article can be found online at: https://www.eurekaselect.com/article/22780We regret the error and apologize to readers.Details of the error and a correction are provided here.