The innate immune system is responsible for the body's defense against aggressive agents, mainly through activating pattern-recognition receptors (PRRs). Recognizing these agents results in an inflammatory response that activates tissue repair and eliminating the agent. Among the macromolecules related to these events are inflammasomes (inflammatory response activators), with emphasis on nucleotide-binding domain leucine-rich repeat-containing receptors protein 3 (NLRP3), in which blocking their oligomerization inhibits inflammasome activity. In this way, targeting NLRP3 represents a new approach to designing anti-inflammatory drugs. Here, molecular docking and dynamics, focusing on Dynamic Cross-Correlation Matrix (DCCM) analysis, were used to characterize significant interactions of MCC950 (known inhibitors) and their analog NP3-166 (ligand co-crystalized) with NLRP3 and generate useful information in drug design. The results showed that the compounds were stable during the MD simulation time (100 ns), demonstrated by the RMSD RMSF, R_g, SASA, and H-bond plots. Analysis of the DCCM graphs showed that more correlated movements are presented for MCC950 compared to NP3-166. In fact, the more rigid structure of MCC950 may influence the more significant interaction. A higher correlation observed in both complexes between residues 100 – 200 and 300 – 400 highlights the results obtained from the interaction analysis, showing that interaction with Ala²²⁸ and Arg⁵⁷⁸ may be essential for the inhibitory activity of the compounds. Our findings highlight that greater structural rigidity of the ligand and interactions with residues Ala²²⁸ and Arg⁵⁷⁸ may be critical for designing new NLRP3 inhibitors with anti-inflammatory potential.

A High performance thin layer chromatographic method for simultaneous estimation of Aliskiren, Amlodipine besylate and Hydrochlorothiazide was developed and validated as per ICH guidelines. Moreover, robustness testing was performed applying a central composite design with k factor having 2 k factorial runs, 2k axial experiments and two center points. High performance thin layer chromatographic separation was performed on aluminium plates precoated with silica gel 60F 254 and acetonitrile: methanol: strong ammonis (10:10:0.1, v/v) as optimized mobile phase. The detection wavelength for simultaneous estimation of three drugs was 250 nm. The Rf values for Aliskiren, Amlodipine besylate and Hydrochlorthiazide were 0.54, 0.32 and 0.78 for, respectively. Percent recoveries in terms of accuracy for the marketed formulation was found to be 101.3-104.4, 100.7-104 and 101.5-103.9 for, Aliskiren, Amlodipine besylate and Hydrochlorthiazide, respectively. The pooled % relative standard deviation values for repeatability studies and intermediate precision studies was found to be less than 2% for Aliskiren, Amlodipine besylate and Hydrochlorthiazide, respectively. All these three factors (methanol content, developing distance and band size) were evaluated in the robustness testing by central composite design and these were found to have an insignificant effect on the retention factor. However, methanol content in total mobile phase as a factor appeared to have significant effect on robustness, compared to band size and developing distance and hence it is important to be carefully controlled. In summary, a novel, simple, accurate and reproducible high performance thin layer chromatographic method was developed, which would be of use in quality control of these tablets.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by multiple factors such as the progressive decline of the levels of the neurotransmitter acetylcholine, and the deregulation of the homeostasis of bio-metals such as copper, zinc and iron.

Acetylcholine is hydrolyzed by acetylcholinesterase and butyrylcholinesterase and the current therapeutic strategies are based on the treatment of AD patients with these enzymes’ inhibitors. Although these strategies are focused on disease’s symptomatic relief, recent studies have shown that the long-term use of these drugs may lead to disease modifying benefits.

The deregulation of the bio-metals’ homeostasis has been related to oxidative stress and to the induction of Ab aggregation and of tau hyperphosphorylation and aggregation.

Since AD is a multifactorial disease, discovering a multi-target drug could be an interesting challenge leading to a disease modifying therapy. In this context, mannosylpurines synthesized in our group already showed a potent butyrylcholinesterase (BChE) inhibition. Aiming at the discovery of such multitarget drug candidates, we have synthesized a new series of mannosyl and rhamnosylpurines and evaluated copper chelation and cholinesterases’ inhibition. The results obtained will be presented and discussed.

Lavandula angustifolia is one of the most popular medicinal plants, rich source of bioactive compounds. Most of the studies on lavender had focused on its essential oil and its use as a sleep aid, calmative, fragrant, insect repellant and flavoring agent. This work is aimed at investigating, for the first time, the potential role of L. angustifolia in the management of metabolic syndrome (MetS), one of the major and escalating public-health and clinical challenge worldwide. Herein, the aerial parts of L. angustifolia, collected in June 2021 in the “Parco Nazionale del Pollino”, Southern Italy, were subjected to extraction by maceration with ethanol. Then, the total extract was partitioned with solvents at different polarity such as n-hexane, dichloromethane and ethyl acetate. Extract and fractions were evaluated for their ability to inhibit alpha-glucosidase as well as lipase. The ethanol extract remarkably inhibited a-glucosidase and lipase (IC₅₀ of 2.55 and 30.50 microg/ml, respectively) better than the positive control acarbose and orlistat (IC₅₀ of 35.51 and 37.12 microg/ml, respectively). The most active fraction was dichloromethane with IC₅₀ of 14.67 and 17.64 mg/ml, against alpha-glucosidase and lipase, respectively. Taking into account obtained results, L. angustifolia could be used for formulation of new products; however, further preclinical studies will be needed to confirm its in vivo efficacy, as well as to prove the safety of the tested extracts and fractions.

Selective modification of natural compounds is one of the most important ways to develop and search for new biologically active substances of various structural types.

It was found earlier that some compounds with octahydro-2H-chromene scaffolds synthesized from monoterpenoid (-)-isopulegol demonstrated promising biological activity, e.g., analgesic, and antiviral activities, inhibitory activity against DNA repair enzyme Tdp1.

The flexible method for the synthesis of octahydro-2H-chromenes derivatives is the Prins cyclization. This reaction could serve also as an initiator of a three-component tandem reaction. For example, the sequence of the Prins and Ritter reactions is one of the best synthetic methods to efficiently build six-membered fragment of 4-amidotetrahydropyran in a one-pot single step reaction.

In this work we have developed a method for synthesis of chiral 4-acetamido-octahydro-2H-chromenes. We used tandem Prins-Ritter reaction between (-)-isopulegol and a set of ketones in acetonitrile. Desired products were formed as a mixture of 4R/4S diastereomers, where 4S one is a major isomer.

Development of new analgesic agents with high activity and low toxicity is important task. It is known that the heterocyclic compounds synthesized from (–)-isopulegol exhibit analgesic activity. In the study of the analgesic activity of the synthesized compounds in vivo, we found that a number of derivatives showed high analgesic activity reliably and not inferior in efficiency to the reference drug sodium diclofenac administered at a similar dose.