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Highlights • Prostate cancer is among the leading causes of death in men where targeting autophagy is of importance in treatment; • Autophagy governs proliferation and metastasis capacity of prostate cancer cells; • Autophagy modulation is of interest in improving the therapeutic response of prostate cancer cells; • Molecular pathways, especially involving non-coding RNAs, regulate autophagy in prostate cancer; • Autophagy possesses both diagnostic and prognostic roles in prostate cancer, with promises for clinical application.

Angiogenesis inhibitors and photosensitizers are pivotal in tumor clinical treatment, yet their utilization is constrained. Herein, eleven novel angiogenesis inhibitors were developed through hybridization strategy to overcome their clinical limitations. These title compounds boast excitation wavelengths within the "therapeutic window", enabling deep tissue penetration. Notably, they could generate superoxide anion radicals via the Type I mechanism, with compound 36 showed the strongest superoxide anion radical generating capacity. Biological evaluation demonstrated remarkable cellular activity of all the title compounds, even under hypoxic conditions. Among them, compound 36 stood out for its superior anti-proliferative activity in both normoxic and hypoxic environments, surpassing individual angiogenesis inhibitors and photosensitizers. Compound 36 induced cell apoptosis via superoxide anion radical generation, devoid of dark toxicity. Molecular docking revealed that the target-recognizing portion of compound 36 was able to insert into the ATP binding pocket of the target protein similar to sorafenib. Collectively, our results suggested that hybridization of angiogenesis inhibitors and photosensitizers was a potential strategy to address the limitations of their clinical use. Discovery of novel angiogenesis inhibitors which could address the clinical limitations of both angiogenesis inhibitors and photosensitizers. [Display omitted] • Novel angiogenesis inhibitors were designed and synthesized through adopting hybridization strategy. • Novel angiogenesis inhibitors could address clinical limitations of both angiogenesis inhibitors and photosensitizers. • Sorafenib might be used as an amplifier to enhance the reactive oxygen generation capacity of photosensitizers. [ABSTRACT FROM AUTHOR]

Prostate cancer is a leading cause of death worldwide and new estimates revealed prostate cancer as the leading cause of death in men in 2021. Therefore, new strategies are pertinent in the treatment of this malignant disease. Macroautophagy/autophagy is a "self-degradation" mechanism capable of facilitating the turnover of long-lived and toxic macromolecules and organelles. Recently, attention has been drawn towards the role of autophagy in cancer and how its modulation provides effective cancer therapy. In the present review, we provide a mechanistic discussion of autophagy in prostate cancer. Autophagy can promote/inhibit proliferation and survival of prostate cancer cells. Besides, metastasis of prostate cancer cells is affected (via induction and inhibition) by autophagy. Autophagy can affect the response of prostate cancer cells to therapy such as chemotherapy and radiotherapy, given the close association between autophagy and apoptosis. Increasing evidence has demonstrated that upstream mediators such as AMPK, non-coding RNAs, KLF5, MTOR and others regulate autophagy in prostate cancer. Anti-tumor compounds, for instance phytochemicals, dually inhibit or induce autophagy in prostate cancer therapy. For improving prostate cancer therapy, nanotherapeutics such as chitosan nanoparticles have been developed. With respect to the context-dependent role of autophagy in prostate cancer, genetic tools such as siRNA and CRISPR-Cas9 can be utilized for targeting autophagic genes. Finally, these findings can be translated into preclinical and clinical studies to improve survival and prognosis of prostate cancer patients. Highlights: • Prostate cancer is among the leading causes of death in men where targeting autophagy is of importance in treatment; • Autophagy governs proliferation and metastasis capacity of prostate cancer cells; • Autophagy modulation is of interest in improving the therapeutic response of prostate cancer cells; • Molecular pathways, especially involving non-coding RNAs, regulate autophagy in prostate cancer; • Autophagy possesses both diagnostic and prognostic roles in prostate cancer, with promises for clinical application. [ABSTRACT FROM AUTHOR]

TRAP1, the mitochondrial component of the Hsp90 family of molecular chaperones, displays important bioenergetic and proteostatic functions. In tumor cells, TRAP1 contributes to shape metabolism, dynamically tuning it with the changing environmental conditions, and to shield from noxious insults. Hence, TRAP1 activity has profound effects on the capability of neoplastic cells to evolve towards more malignant phenotypes. Here, we discuss our knowledge on the biochemical functions of TRAP1 in the context of a growing tumor mass, and we analyze the possibility of targeting its chaperone functions for developing novel anti-neoplastic approaches. [ABSTRACT FROM AUTHOR]

The biological applications of germylenes remain unrealised owing to their unstable nature. We report the isolation of air‐, water‐, and culture‐medium‐stable germylene DPMGeOH (3; DPM=dipyrromethene ligand) and its potential biological application. Compound 3 exhibits antiproliferative effects comparable to that of cisplatin in human cancer cells. The cytotoxicity of compound 3 on normal epithelial cells is minimal and is similar to that of the currently used anticancer drugs. These findings provide a framework for a plethora of biological studies using germylenes and have important implications for low‐valent main‐group chemistry. [ABSTRACT FROM AUTHOR]

A large number of structures of anti-cancer drug targets have been solved and deposited to the protein data bank already. Identification of the targets for marine compounds with anti-tumor activity presents a challenge for marine natural products scientists. In this study, fast and efficient computational reverse docking was applied to predict the probable targeting proteins of the marine compounds with anti-tumor activity. Crystal structures of the proteins involved in tumor genesis, growth and metastasis were collected from PDB to construct the anti-tumor protein database (APD) for reverse docking. Two non-commercial docking programs, AutoDock Vina and LeDock, were used to perform the docking. Our results suggest that reverse docking is efficient for target fishing of compounds with known anti-tumor activities. In addition, the results show that performance of reverse docking using LeDock is superior to that using AutoDock Vina. Overall, reverse docking is a fast and efficient computational method to identify the probable target of the compounds with anti-tumor activities, and it can be complementary to the biological testing methods. [ABSTRACT FROM AUTHOR]

Abstract: Three novel inosine-based dinuclear platinum complexes have been synthesized via a solid-phase strategy. In these compounds, the metal is linked both to the N-7 of the purine nucleus and to the terminal amine group of a hexylamine side chain installed on N-1. Cis- or trans- diamine as well as ethylenediamine ligands are coordinated to platinum along with a chloride. The synthesised complexes were tested against four different human tumor cell lines. One of these complexes proved to be more cytotoxic than cisplatin against the MCF7 cancer cell line in a short-term exposure assay. [Copyright &y& Elsevier]

Abstract: This review provides a substantial knowledge on the action mode of organotins in cancer chemotherapy. The coordinating ability of organotin compounds towards DNA and cancer cells is discussed. Most of the organotins tested are DNA-targeted and mitotic, the action mode occurring via a gene-mediated pathway. These potential anti-cancer drugs are actually being studied widely, and whilst they are efficacious and perhaps curative against a select number of neoplasias, suffer from a variety of deficiencies, notably severe systemic toxicity and a tendency to elicit drug resistance. [Copyright &y& Elsevier]

Abstract: An enantiodivergent synthesis of both enantiomers of methylenolactocin is described through stereocontrolled addition of n-pentyl magnesium bromide to two d-mannitol-derived diastereomerically related aldehydes having an α-chiral center with a β hetero atom. [Copyright &y& Elsevier]