Mohammad Abdel-Halim

1. Corneal injury is a critical ocular emergency that can threaten a patient’s sight, characterized by a breach in the corneal epithelium that extends into the underlying stroma. Even when medical ...

The spiroindoline framework is a privileged scaffold in medicinal chemistry, appearing in natural products and in synthetic bioactive compounds, such as BAY 1214784, RO8994, and RK-287107, with reported activities ranging from antimitotic effects to kinase inhibition. This review covers the methods developed between 2020 and 2025 for constructing spiroindoline frameworks, organized first by the site of spirocyclization (C2 versus C3 of the indole) and then by catalyst class: second- and third-row transition metals, first-row transition metals and main-group Lewis acids, organocatalysis, and visible-light photoredox. For each method we discuss the reaction design, the accessible substrate scope, and mechanistic insights, with particular attention to how stereochemistry is controlled. We also highlight representative downstream transformations that demonstrate the synthetic utility of the produced spiroindolines. Progress over the past five years has been substantial, particularly in enantioselective methods that create a single stereocenter and in cascade designs that build complex polycyclic frameworks in a single operation. Asymmetric construction of multiple adjacent stereocenters, gram-scale demonstrations, and genuinely sustainable conditions remain less developed; these areas are priorities for future work.

Cancer immunotherapy enhances the body's ability to recognize and eliminate tumor cells, mainly by modulating immune checkpoints such as PD‐1/PD‐L1 and CTLA‐4. Monoclonal antibody inhibitors targeting PD‐1 or PD‐L1 have transformed cancer care, but their high cost, IV administration, and immune‐related toxicities have encouraged the development of small‐molecule alternatives. Early PD‐L1 small‐molecule inhibitors, pioneered by Bristol Myers Squibb, block PD‐1/PD‐L1 interactions by occupying hydrophobic pockets on PD‐L1, and SAR studies continue to refine their potency and selectivity. This review focuses on how the structural scaffolds of small‐molecule PD‐L1 inhibitors determine their mechanisms of action, protein interactions, and biological performance. We examine how different chemotypes influence dimerization of PD‐L1, disruption of PD‐1 binding, or engagement of additional immune‐modulatory pathways. Special attention is given to scaffolds capable of acting through more than one mechanism, as these may offer broader or more durable immunomodulatory effects. We also compare how scaffold design correlates with activity across in vitro assays, co‐culture immune models, and in vivo tumor systems, highlighting the physicochemical features that enable or limit translatability. Finally, we discuss emerging clinical efforts, the challenges underlying trial failures, and how refined structural design may guide the next generation of small‐molecule PD‐L1 inhibitors.

A series of chalcone-based derivatives were synthesized and assessed for their ability to target neutrophil-driven inflammation. Strategic modifications on the 1,3-diaryl-prop-2-en-1-one scaffold, all bearing a methoxylated ring B, revealed two distinct anti-inflammatory profiles: inhibitors of both superoxide (SO) generation and elastase release, and selective SO inhibitors. Compound 17, featuring 3-methoxy and 2,4-dichlorophenyl substitutions, demonstrated the most potent dual inhibition (IC₅₀ = 1.17 µM for SO and 2.60 µM for elastase), while compound 15 selectively suppressed SO production (IC₅₀ = 2.63 µM) with minimal elastase impact. Compound 17 hampered neutrophil migration without inducing cytotoxicity, and mechanistically inhibited the phosphorylation of JNK, ERK, and FAK/paxillin—key signaling pathways in neutrophil migration and activation, without altering calcium flux. These findings highlight compound 17 as a promising lead for targeting neutrophil-mediated inflammatory disorders and underscore the potential of chalcone scaffolds for precise immunomodulation.

A novel series of pyrazolidinones and pyrazolidinediones was developed as selective COX-2 inhibitors, exhibiting anti-amyloid β, anti-tau, and neuroprotective activities.