The synthesis and biological evaluation of brassinosteroids (BRs) analogs with chemical modification in the side alkyl chain is a matter of current interest. Recently, a series of BR analogs with phenyl or benzoate groups in the alkyl chain have been reported. The effect of substitution in the aromatic ring on the biological activities of these new analogs has been evaluated, and the results suggest that the bioactivity is enhanced by substitution with an F atom. In this context, we have synthesized, characterized, and evaluated a series of new analogs of 23,24-bisnorcholenic type in which the benzoate group at the C-22 position is substituted with an F atom at “ortho or para” positions. Plant growth-promoting activities were evaluated by using the rice lamina inclination test and bean second internode biotest. The results obtained with both bioassays indicate that the compound with an F atom in the para position on the aromatic ring is the most active BR analog and in some cases is even more active than brassinolide. The docking study confirmed that compounds with an F atom adopt an orientation similar to that predicted for brassinolide, and the F atom in the “para” position generates an extra hydrogen bond in the predicted binding position.

Brassinosteroids (BRs) are an important group of polyhydroxylated naturally occurring steroidal phytohormones found in the plant kingdom in extremely low amounts. Due to the low concentrations in which these compounds are found, much effort has been dedicated to synthesizing these compounds or their structural analogs using natural and abundant sterols. In this work, we report the synthesis of new brassinosteroid analogs obtained from hyodeoxycholic acid, with a 3,6 dioxo function, 24-Nor-22(S)-hydroxy side chain and p-substituted benzoate function at C-23. The plant growth activities of these compounds were evaluated by two different bioassays: rice lamina inclination test (RLIT) and BSI. The results show that BRs’ analog with p-Br (compound 41f) in the aromatic ring was the most active at 1 × 10⁻⁸ M in the RLIT and BSI assays. These results are discussed in terms of the chemical structure and nature of benzoate substituents at the para position. Electron-withdrawing and size effects seems to be the most important factor in determining activities in the RLIT assay. These results could be useful to propose a new structural requirement for bioactivity in brassinosteroid analogs.

The phytopathogenic fungus Botrytis cinerea, which causes gray mold disease, has become a limiting factor on agricultural production. B. cinerea field control is made mainly using chemical fungicides, which has led to the spreading of resistant populations of this fungus. Thus, the quest of new fungicides molecules has been focused on synthesis of natural product-inspired compounds. The main aim of this work is to synthesize prenylated phenol derivatives and to assess their potential application as antifungal agents with minimal phytotoxic effects. Thus, new prenylphenols (4, 5, and 7) have been obtained by microwave irradiation with yields ranging from 2.4% to 42.9%, whereas compounds 8 and 9 were synthesized with yields of 25.6% and 54.1%, respectively. The effect of different concentrations of these compounds on B. cinerea spore germination, and their phytotoxic effect on tomato (Solanum lycopersicum L.) seed germination and root growth, were evaluated. Obtained results indicate that biological activities of all tested compounds are concentration-dependent. Interestingly, compound 7 exhibits the highest antifungal activity against B. cinerea spores (IC₅₀ < 50 µg/mL) with minimal phytotoxicity on tomato seed germination and root growth. In contrast, compounds 2 and 3 are active against spores (IC₅₀ = 461 and 325 µg/mL, respectively) but, at the same time, their phytotoxicity is important at the highest concentrations. These results indicated that the presence of hydroxyl and methyl substituents on the aromatic ring of these compounds induces variations in biological activities, and compound 7 could be a promising candidate as a sporicidal agent.

Background: Alzheimer’s disease (AD) is a complex neurodegenerative disorder and a major global health challenge. The traditional “one drug–one target” paradigm has shown limitations in addressing its multifactorial nature. Multitarget-directed ligands (MTDLs), designed to modulate multiple pathological pathways, have emerged as a promising therapeutic strategy. Objectives: To examine the structural, thematic, and temporal evolution of multitarget strategies for AD treatment between 2006 and 2025. Methods: A total of 1184 Web of Science-indexed articles were analyzed. Publication growth, h-index, author productivity, institutional and national contributions, and keyword co-occurrence networks were evaluated using VOSviewer. Bibliometric laws (Price, Bradford, Zipf, and Lotka) were applied to characterize productivity patterns and thematic organization. Results: Multitarget research shows exponential growth, suggesting a consolidation of the MTDL paradigm. China, India, the United States, Italy, and Spain were the most productive countries. Early studies focused on cholinesterase inhibition, particularly acetylcholinesterase-based hybrids. The field expanded to include β-amyloid aggregation, oxidative stress, metal chelation, and blood–brain barrier permeability. Recent trends emphasize integration of computational approaches, including molecular docking, molecular dynamics, virtual screening, and network pharmacology, alongside targets such as BACE1 and GSK-3β. Conclusions: Multitarget strategies have evolved toward a systems-oriented framework. Despite advances, challenges remain in reducing cholinesterase dependency and improving translational validation. This study provides a framework to interpret therapeutic evolution and guide future network-based drug design.

Background: Autism spectrum disorder (ASD) represents a major challenge in neurological development research and is receiving increasing attention from the pharmacological and pharmaceutical sciences. Despite this constant growth, there is no document that provides a comprehensive overview integrating publication trends, key contributors, and thematic developments, allowing efforts to be focused on specific areas. Objective: To conduct a comprehensive bibliometric analysis of pharmacological research related to ASD published between 2001 and 2025. Methods: The database obtained contains 1170 articles indexed in the Web of Science (WoS) database in the JCR Pharmacy and Pharmacology category. Bibliometric indicators such as publication growth, h-index, authorship, institutional and national productivity, and keyword co-occurrence were analyzed using VOSviewer and the laws of Price, Bradford, Zipf, and Lotka. Results: A total of 1170 documents were analyzed, showing an exponential increase in pharmacological research related to ASD over the last two decades. The United States, China, and Italy emerged as the most productive countries, while King Saud University, Harvard Medical School, and The Ohio State University were among the leading institutions. The most frequently cited keywords, such as “autism spectrum disorder,” “valproic acid,” “oxidative stress,” and “flavonoids,” revealed a translational approach linking neurobiological mechanisms, redox imbalance, and therapeutic interventions. Contemporary research emphasizes immuno–synaptic interactions, microbiota, and biomarker-guided approaches. Conclusions: This study highlights the global expansion and diversification of pharmacological research in ASD. The results underscore a shift toward integrated biological frameworks and precision-oriented strategies, reinforcing the need for interdisciplinary collaboration to advance translational outcomes in ASD therapy.

The synthesis and structural characterization of new brassinosteroid (BR) analogs, in which substituents with different electronegativities and molecular sizes have been attached to a C-22 benzoate function, are described. The biological activities of all new compounds were evaluated by using the rice lamina inclination test (RLIT) and inhibition of root growth of Arabidopsis thaliana . The RLIT data is compared with those previously reported for two series of compounds having the same substitution pattern at C-22 but different structure in ring A. This comparison revealed that a 2α,3α-dihydroxy configuration is more active than a 3-carbonyl or 3β-hydroxy function in this ring. Additionally, the accumulation of the dephosphorylated form of the BES1 protein, which is part of the BRs signaling pathway and control their activity, has been evaluated as well. The results are analyzed in terms of BR analog’s structure and compared with binding energies obtained from a docking study. In this way, it is intended to assess the effect of chemical structure on the initial and one intermediate step, and on the final plant response. Our results show that the binding of BR analogs to the active site, which initiate the signaling process, and dephosphorylation of BES1 depend on the structure of BR analogs in a similar way. However, the relationship between the BR analog’s structure and the final plant response is different. The dependence on unknown factors which are able to activate or repress genes associated with growth and development is discussed.