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Simple Summary: A promising approach to combat aggressive prostate cancer involves androgen receptor degraders, which break down the crucial protein driving cancer progression. In contrast to traditional drugs, these degraders offer a potential solution to drug resistance. Methods like PROTACs have shown promise in reducing androgen receptor levels in cells and clinical benefits in patients. Six PROTACs and two other degraders have entered early clinical trials for potential treatment. While progress has been made in understanding these degraders, it is essential to stay updated on emerging developments. This article provides an overview of advancements in this field since 2020. Induced protein degradation has emerged as an innovative drug discovery approach, complementary to the classical method of suppressing protein function. The androgen receptor signaling pathway has been identified as the primary driving force in the development and progression of lethal castration-resistant prostate cancer. Since androgen receptor degraders function differently from androgen receptor antagonists, they hold the promise to overcome the drug resistance challenges faced by current therapeutics. Proteolysis-targeting chimeras (PROTACs), monomeric degraders, hydrophobic tagging, molecular glues, and autophagic degradation have demonstrated their capability in downregulating intracellular androgen receptor concentrations. The potential of these androgen receptor degraders to treat castration-resistant prostate cancer is substantiated by the advancement of six PROTACs and two monomeric androgen receptor degraders into phase I or II clinical trials. Although the chemical structures, in vitro and in vivo data, and degradation mechanisms of androgen receptor degraders have been reviewed, it is crucial to stay updated on recent advances in this field as novel androgen receptor degraders and new strategies continue to emerge. This review thus provides insight into recent advancements in this paradigm, offering an overview of the progress made since 2020. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is one of topmost health concerns, and metastatic castration-resistant prostate cancer is the fatal form. Two taxanes, docetaxel and cabazitaxel, are the only two FDA-approved chemotherapeutics that can provide survival benefits to patients with the lethal version of prostate cancer. Taxanes, alongside numerous other naturally occurring products, can promote the assembly and stability of microtubules to halt cell division and promote various cancer cell deaths. Additionally, this group of compounds, named microtubule stabilizing agents, can impede the androgen–androgen receptor complex from moving into the cell nucleus, conquering androgen receptor-containing prostate cancer cell proliferation and metastasis. This review aims to overview the preclinical and clinical studies, clinical uses, and the mechanisms of action of microtubule-stabilizing agents as anti-prostate cancer agents. A variety of microtubule-stabilizing cytotoxic agents (MSA) with diverse chemical scaffolds have been discovered from marine sponges, microorganisms, and plants. Two MSAs, docetaxel and cabazitaxel, are the exclusive chemotherapeutics that convey a survival benefit in patients with castration-resistant prostate cancer (CRPC). Additional MSAs have been investigated for their potential in treating prostate cancer in both clinical and preclinical settings. Independent of promoting mitotic arrest, MSAs can suppress the nuclear accumulation of androgen receptor (AR), which is the driving force for prostate cancer cell growth and progression. The alternative mechanism not only helps to better understand the clinical efficacy of docetaxel and cabazitaxel for AR-driven CRPC but also provides an avenue to seek better treatments for various forms of prostate cancer. The dual mechanisms of action enable MSAs to suppress AR-null prostate cancer cell proliferation by cell mitosis pathway and to interfere with the AR signaling pathway in AR positive cells. MSA chemotherapeutics, being administered alone or in combination with other therapeutics, may serve as the optimal therapeutic option for patients with either castration-sensitive or castration-resistant prostate cancer. This review provides an overview of the anti-prostate cancer profiles (including preclinical and clinical studies, and clinical use) of diverse MSAs, as well as the mechanism of action. [ABSTRACT FROM AUTHOR]

Present herein is the first example of aluminium nanoring assembly by fatty acids. And the auxiliary alcohol sites can be modified either by monohydric alcohols (AlOC-33 to AlOC-35) or diols (AlOC-36 to AlOC-38). The monohydric alcohol modified ten-membered aluminium (Al10) rings are coplanar, while the diol modified ones possess a saddle-shaped configuration. Interestingly, the diol modified Al10 ring (AlOC-36) can convert into a coplanar ring (AlOC-33-B). AlOC-33-B possesses a similar molecular structure but a different supramolecular structure with AlOC-33. The structural transformation is confirmed to be a thermodynamically spontaneous process through density-functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

The regioselective demethylations of two C19-diterpenoid alkaloids, 2 and 3, have been achieved with HBr-HOAc, trimethylsilyl iodide, or BBr3. It was observed that HBr-HOAc is an optimal demethylating agent for these two C19-diterpenoid alkaloids because it could provide different O-demethylation products by using different reaction temperature and reaction time. Especially, 1-O-methyl group in 2 and 3, one of the most difficult ones to be demethylated, could be removed by the treatment with HBr-HOAc at an elevated temperature and a prolonged reaction time. [ABSTRACT FROM AUTHOR]

The conversional synthesis of taxoids by the BAC sequence from the C19-diterpenoid alkaloids, 14-acetyltalatisamine (1), yunaconitine (12), and 14-acetylchasmanine (19), was designed and explored. Two aconane-type diterpenes 17 and 28, the advanced intermediates for our conversional synthesis, were synthesized. The key steps include the rupture of the C(7)-C(17) bond, the formation of imine, and the denitrogenation. [ABSTRACT FROM AUTHOR]

The asymmetric unit of the title compound, (C2H10N2)2[Ti4O4(C6H6NO6)4], consists of halves of two centrosymmetric tetrameric [Ti4O4{N(CH2COO)3}4]4− anions, two [H3N(CH2)2NH3]2+ cations and a disordered mol­ecule of water of crystallization. In the [Ti4O4{N(CH2COO)3}4]4− tetramer, each Ti atom is coord­inated by one nitrilo­tri­acetate ligand and two μ-oxo ligands, so that four titanium and four μ-O atoms form an eight-membered ring. The tetramers are connected by hydrogen bonds with [H3N(CH2)2NH3]2+ cations and with water mol­ecules, leading to an intricate three-dimensional network. [ABSTRACT FROM AUTHOR]

The O-acyl group at C-1 of two C19-diterpenoid alkaloids 2 and 5 was transferred to the secondary amine nitrogen to form amides 3 and 6 in the basic condition. This kind of O-to-N intramolecular acyl migration could be caused by the near distance between the nucleophilic nitrogen atom and the carbonyl group of the ester at C-1 in the C19-diterpenoid alkaloids, which is consistent with the conformation of rings A and E in the C19-diterpenoid alkaloids. [ABSTRACT FROM AUTHOR]

The first biomimetic conversion from the aconitine-type C19-diterpenoid alkaloids to the corresponding alkaloids of lactone-type C19-diterpenoid alkaloid has been achieved. Chasmanine was used as starting material with Baeyer–Villiger oxidation as a key reaction. It was also observed that the oxygenated group at C-16 did not change the relative migration tendencies of C-13 and C-9 during the oxidation. Meantime, a novel D-ring fragmented compound was obtained during the course of the present investigation. The plausible mechanism of the formation of this compound was also proposed. [ABSTRACT FROM AUTHOR]

Abstract: Pyrolysis of carboxylic acid group at C-4 of 2, an oxidation product from the C19-diterpenoid alkaloid lycoctonine 1, generated an unexpected but novel rearranged product 13 (37%). The structure of 13 was confirmed by its 2D NMR data and its single crystal X-ray crystallographic analysis. In addition, hydrogenolysis of 13 in the presence of acetic acid yielded the N–C6 bond fission products 16 and 17, which represents the first hydrogenolysis involving the breakage of the N–C6 bond of the diterpenoid alkaloids. Some new observations on the oxidation of lycoctonine 1 were described as well. [ABSTRACT FROM AUTHOR]

Abstract: We have corrected (Tetrahedron 2013, 69, 5859–5866) the structures of diterpenoid alkaloids reported in the Journal of Natural Products 2012, 75, 1145–1159. Our follow-up experiments compel us to present further revisions and clarifications on the diterpenoid alkaloids: (1) The naturally occurring forms of carmichaelines B, C, and D in Shi's paper (Journal of Natural Products 2012, 75, 1145–1159) are neither quaternary ammonium hydroxides 2–4 nor the initially revised trifluoroacetates. They are indeed the vakognavine-type C20-diterpenoid alkaloids 11–13. (2) The samples' concentration is the critical factor to the signals' intensity for F3CCOO− in the alkaloid trifluoroacetates. Incorporation of TFA into the corresponding salts resulted in signals' enhancement due to the closeness of δ values (∼116 ppm, ∼159 ppm) of free TFA and those of F3CCOO−. After removal of free TFA, the carbon signals of CF3COO− could become weaker, but their chemical shifts remained almost unchanged. The possible reason might be the ionization of TFA in acetone. (3) The NMR data cannot distinguish TFA from trifluoroacetates (e.g., F3CCOONa and C19-diterpenoid alkaloid trifluoroacetates), indicating that the signal at around δ −76 cannot be used to exclude the existence of trifluoroacetates. In addition to the NMR and CSI-MS data, 1H–15N HMBC technique was also used to distinguish the free alkaloids from their trifluoroacetates. (4) The X-ray crystallographic analysis of compound 20 confirmed that the ‘new alkaloid’ (-b) in the Shi's paper is indeed the known compound aconifine trifluoroacetate. (5) Collectively, Shi's paper mixed-up the free alkaloids with their salts and the concepts of structure and conformation. Naming different structures with A-b and A-c is also confusing. [Copyright &y& Elsevier]

The relative reactivity of three hydroxyl groups in aconitine toward acetylation, chlorination, sulfonylation, and oxidation has been studied in this paper. The reduction of C-3 ketone and C-15 ketone derivatives of aconitine was also investigated. It was found that (1) the relative reactivity of three hydroxyl groups toward acetylation, chlorination, and sulfonylation is 3-OH>13-OH>>15-OH; (2) 3-OH is much more reactive than 15-OH toward oxidation; and (3) reduction of the carbonyl group at C-3 with NaBH4 generated a pair of C-3 epimers, while the reduction products of the carbonyl group at C-15 depend largely on the specific reducing agent and the absolute configuration of 16-OCH3. When the substrate has 16β-OCH3, its carbonyl group at C-15 can be reduced with NaBH4 to yield exclusively the 15α-OH-containing product. Upon replacement of reducing agent NaBH4 with LiAlH4, the C-15 carbonyl group can be reduced to yield a pair of C-15 epimers. On the other hand, when the substrate has 16α-OCH3, C-15 carbonyl group can only be reduced to generate 15α-OH-containing product. [ABSTRACT FROM AUTHOR]

A series of new bisbenzylisoquinoline alkaloids was partially synthesized from tetrandrine and fangchinoline and evaluated for their ability to reverse P-glycoprotein-mediated multidrug resistance (MDR) in cancer cells. All the test compounds increased the intracellular accumulation rate of rhodamine 123 in MDR cells (Bel7402 and HCT8), and most exhibited more potent MDR-reversing activity relative to the reference compound verapamil. Compounds 8, 10, 13, and 14 enhanced intracellular accumulation of doxorubicin in Bel7402 and HCT8 cells. [ABSTRACT FROM AUTHOR]

Abstract: A theoretical study of the structural, elastic and electronic properties of spinel LiTi2O4 anode has been performed by density functional theory (DFT) plane-wave pseudopotential method. The independent elastic constants, shear modulus (G), bulk modulus (B), and Young''s modulus (E) are evaluated, respectively. The results suggest that cubic LiTi2O4 is mechanically stable. The G/B ratio of 0.584 indicates the ductility of LiTi2O4 is good. The electron density difference of LiTi2O4 shows that the O2p orbits overlap effectively with Ti3d ones, confirming the formations of strong covalent bonds between them, while Li is fully ionized in the lattice. The formation enthalpy for LiTi2O4 is calculated to be −2070.723±1.6kJmol−1. The strong covalent bonds between O and Ti atoms are not only responsible for the excellent mechanical stabilities but also very crucial for the thermodynamic stability of LiTi2O4 compound. Furthermore, in Li2Ti2O4 compound, the full occupation of 16(c) sites by Li+ not only leads to a smaller C 12 value but also leads to a much larger C 44 one. Therefore, the plasticity and ductility of the Li2Ti2O4 become poor in comparison to LiTi2O4, while the thermodynamic stability of Li2Ti2O4 can be further improved after the Li+ intercalation of LiTi2O4. [Copyright &y& Elsevier]

Abstract: Optical properties and structural aspects of As x S100-x glasses from visible to terahertz wavelengths were explored. A series of annealed, bulk As x S100-x glasses (x =30 to 42) were made and their refractive indices determined at terahertz, infrared, and visible frequencies using a quasi-optical backwards wave oscillator spectrometer for terahertz measurements combined with a prism coupler for visible and infrared measurements. It was found that the refractive index at all frequencies increases with arsenic composition up to 40at.% arsenic and then decreases with additional arsenic. The structure in X-ray diffraction patterns supports the notion of a minimum volume at 40at.%, while the average covalent coordination number indicates that the rigidity percolation threshold is reached there. At arsenic concentrations >40at.%, the network becomes over-constrained, and the molar volume increases. [Copyright &y& Elsevier]