Herein, we review the recent progress in the synthesis of representative nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and naproxen. Although these drugs were discovered over 50 years ago, novel practical and asymmetric approaches are still being developed for their synthesis. In addition, this endeavor has enabled access to more potent and selective derivatives from the key frameworks of ibuprofen and naproxen. The development of a synthetic route to ibuprofen and naproxen over the last 10 years is summarized, including developing methodologies, finding novel synthetic routes, and applying continuous-flow chemistry.

The widespread and uncontrollable emergence of antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, has promoted a wave of efforts to discover a new generation of antibiotics that prevent or treat bacterial infections neither as bactericides nor bacteriostats. Due to its crucial role in virulence and its nonessentiality in bacterial survival, sortase A has been considered as a great target for new antibiotics. Sortase A inhibitors have emerged as promising alternative antivirulence agents against bacteria. Herein, the structural and preparative aspects of some small synthetic organic compounds that block the pathogenic action of sortase A have been described.

Spleen tyrosine kinase (SYK) is an essential mediator of immune cell signaling and has been anticipated as a therapeutic target for autoimmune diseases, notably rheumatoid arthritis, allergic rhinitis, asthma, and cancers. Significant attempts have been undertaken in recent years to develop SYK inhibitors; however, limited success has been achieved due to poor pharmacokinetics and adverse effects of inhibitors. The primary goal of this research was to identify potential inhibitors having high affinity, selectivity based on key molecular interactions, and good drug-like properties than the available inhibitor, fostamatinib. In this study, a 3D-QSAR model was built for SYK based on known inhibitor IC₅₀ values. The best pharmacophore model was then used as a 3D query to screen a drug-like database to retrieve hits with novel chemical scaffolds. The obtained compounds were subjected to binding affinity prediction using the molecular docking approach, and the results were subsequently validated using molecular dynamics (MD) simulations. The simulated compounds were ranked according to binding free energy (ΔG), and the binding affinity was compared with fostamatinib. The binding mode analysis of selected compounds revealed that the hit compounds form hydrogen bond interactions with hinge region residue Ala451, glycine-rich loop residue Lys375, Ser379, and DFG motif Asp512. Identified hits were also observed to form a desirable interaction with Pro455 and Asn457, the rare feature observed in SYK inhibitors. Therefore, we argue that identified hit compounds ZINC98363745, ZINC98365358, ZINC98364133, and ZINC08789982 may help in drug design against SYK.

Considering the potential bioactivities of natural product and natural product-like compounds with highly complex and diverse structures, the screening of collections and small-molecule libraries for high-throughput screening (HTS) and high-content screening (HCS) has emerged as a powerful tool in the development of novel therapeutic agents. Herein, we review the recent advances in divergent synthetic approaches such as complexity-to-diversity (Ctd) and biomimetic strategies for the generation of structurally complex and diverse indole-based natural product and natural product-like small-molecule libraries.

Cysteine–cysteine chemokine receptor 5 (CCR5) has been discovered as a co-receptor for cellular entry of human immunodeficiency virus (HIV). Moreover, the role of CCR5 in a variety of cancers and various inflammatory responses was also discovered. Despite the fact that several CCR5 antagonists have been investigated in clinical trials, only Maraviroc has been licensed for use in the treatment of HIV patients. This indicates that there is a need for novel CCR5 antagonists. Keeping this in mind, the present study was designed. The active CCR5 inhibitors with known IC₅₀ value were selected from the literature and utilized to develop a ligand-based common feature pharmacophore model. The validated pharmacophore model was further used for virtual screening of drug-like databases obtained from the Asinex, Specs, InterBioScreen, and Eximed chemical libraries. Utilizing computational methods such as molecular docking studies, molecular dynamics simulations, and binding free energy calculation, the binding mechanism of selected inhibitors was established. The identified Hits not only showed better binding energy when compared to Maraviroc, but also formed stable interactions with the key residues and showed stable behavior throughout the 100 ns MD simulation. Our findings suggest that Hit1 and Hit2 may be potential candidates for CCR5 inhibition, and, therefore, can be considered for further CCR5 inhibition programs.

A great effort to discover new therapeutic ingredients is often initiated through the discovery of the existence of novel marine natural products. Since substances produced by the marine environment might be structurally more complex and unique than terrestrial natural products, there have been cases of misassignments of their structures despite the availability of modern spectroscopic and computational chemistry techniques. When it comes to refutation to erroneously or tentatively proposed structures empirical preparations through organic chemical synthesis has the greatest contribution along with close and sophiscated inspection of spectroscopic data. Herein, we analyzed the total synthetic studies that have decisively achieved in revelation of errors, ambiguities, or incompleteness of the isolated structures of marine natural products covering the period from 2018 to 2021.