Many of the drugs used in treatment today have been designed based on the “specificity paradigm”. Resistance has developed against drugs designed using this approach, leading to a decrease in their effectiveness. In addition, it is well‐documented in the literature that diseases with complex etiologies, such as Alzheimer's, Parkinson's, and cancer are influenced by multiple genetic and/or environmental factors. As a result, specificity paradigm is often insufficient for treating these diseases. Therefore, there is a need to develop drugs that interact with multiple targets simultaneously through different mechanisms. This review aims to provide an overview of the methods used in multitarget drug design, the reactions employed in the synthesis of these drugs, their applications, and recent research conducted in this field.

The synthesis and biological assessment of novel multi-functionalized pyrrolidine-containing benzenesulfonamides were reported along with their antimicrobial, antifungal, CAs inhibition, and AChE inhibition as well as DNA-binding effects. The chemical structure of the compounds was elucidated by using FTIR, NMR, and HRMS. Compound 3b, which had Ki values of 17.61 ± 3.58 nM (hCA I) and 5.14 ± 0.61 nM (hCA II), was found the be the most potent CAs inhibitor. Compounds 6a and 6b showed remarkable AChE inhibition effects with Ki values 22.34 ± 4.53 nM and 27.21 ± 3.96 nM in comparison to tacrine. Compounds 6a-6c had moderate antituberculosis effect on M. tuberculosis with a MIC value of 15.62 μg/ml. Compounds had weaker antifungal and antibacterial activity in the range of MIC 500-62.5 μg/ml against standard bacterial and fungal strains. Besides these above, molecular docking studies were performed to examine and evaluate the interaction of the remarkable compounds (3b, 6a and 6b) against the current enzymes (CAs and AChE). Novel compounds gained interest in terms of enzyme inhibitory potencies. Therefore, the most potent enzyme inhibitors may be considered lead compounds to be modified for further research.Communicated by Ramaswamy H. Sarma.

To design, synthesize, and evaluate pyrrolidine-based hybrids bearing indole, thiourea, and vinyl sulfone pharmacophores as dual inhibitors of human carbonic anhydrase I/II (hCAI/II) and acetylcholinesterase (AChE), with secondary profiling of complementary bioactivities. Three hybrids (6a, 6b, 8) were obtained via imine azomethine ylide 1,3-dipolar cycloaddition and derivatization. Structures were confirmed spectroscopically and assayed in vitro for hCAI/II and AChE inhibition. Additional evaluations included antioxidant (DPPH), antibacterial, antifungal, antituberculosis (M. tuberculosis H37Rv), cytotoxicity (HCT116, DPSCs), anti-inflammatory (COX-2, SOD1 ELISA, mouse xylene-induced), antidepressant (forced swim test), molecular docking, and in silico ADMET. Compound 6b was the most potent inhibitor (hCAII Ki 75.79 ± 2.83 nM, AChE Ki 43.17 ± 10.44 nM), outperforming acetazolamide (Ki 299.33 ± 45.44 nM) and tacrine (Ki 103.47 ± 11.54 nM). Compound 6a showed the strongest antioxidant effect (72.30% DPPH), antibacterial activity against A. baumannii (MIC 125 µg/ml, comparable to ampicillin), and superior anti-TB potency (MIC 31.25 µg/ml). Compound 6b exhibited stronger antibacterial activity (MIC 62.5 µg/ml). Both reduced COX-2 levels, and 6a increased SOD1. The hybrids were selectively cytotoxic to HCT116, sparing DPSCs. Docking studies confirmed key binding interactions, while ADMET predicted favorable profiles. . The hybrids validate a focused dual-target strategy. Compound 6b is the most potent hCAII and AChE inhibitor, while 6a emerges as a broader multi-target lead with antioxidant, antimicrobial, anti-inflammatory, and antidepressant potential.

The science of pharmacology investigates the effects of drugs on living organisms and vice versa. The frequency of side effects of some drugs used in traditional pharmacological treatment approaches and/or their inability to provide adequate treatment has led to the importance of new drug research and development (R&D) studies. Recently, due to the discovery that some diseases are associated with an imbalanced microbiota (dysbiosis), there has been a surge of interest in therapeutic approaches that can restore balance (biosis) to the microbiota. This review discusses the current status of the pharmabiotic potential of probiotics, prebiotics, synbiotics, paraprobiotics, postbiotics, metabiotics, next-generation probiotics, and fecal microbiota transplantation; describes their pharmacological functions from gastrointestinal disorders to neurodegenerative diseases; and also discusses the developments in pharmaceutical applications of probiotics and their derivatives.

Fermented dairy products such as yoghurt, kefir and cheese are increasingly recognised as functional foods due to the metabolic activity of lactic acid bacteria and the associated microbial communities, including probiotics. During dairy fermentation, these microorganisms generate bioactive compounds, such as bioactive peptides, exopolysaccharides, organic acids and other metabolites, which may contribute to host health. There is emerging evidence that fermented dairy products can influence gastrointestinal function, immune regulation, metabolic health and cardiovascular risk, via mechanisms involving modulation of the gut microbiota, stabilisation of the epithelial barrier and inflammatory signalling pathways. In addition, fermentation may improve lactose digestion, enhance nutrient bioavailability, and generate peptides with anti-hypertensive or antioxidant properties. However, translating these results into consistent health benefits is challenging due to the significant variability in microbial strains, product composition, processing conditions and dosage. Safety considerations such as biogenic amines, sodium content, allergenicity and antimicrobial resistance also require careful monitoring. Future progress in this field will depend on improved product characterisation, strain-level identification and well-designed human intervention studies that integrate multi-omics approaches. In conclusion, fermented dairy products show great potential as a source of bioactive compounds, but more robust clinical evidence and standardised methodologies are required to firmly establish their role in promoting human health.