Like other plant parts, leaves of Carica papaya L. (belongs to family Caricaceae) have a high content of phytochemicals that not only have beneficial food nutritional values but also medicinal potential such as against dengue. Flavonols (clitorin and manghaslin) detected in the C. papaya leaf juice were the subjects of interest in this study which also evaluated their antioxidant profile via electron radical scavenging assays. The leaf juice obtained was subjected to sequential chromatography processes (liquid-liquid extraction and centrifugal partition chromatography) to identify the presence of targeted compounds (clitorin and manghaslin) in the juice. The separation work was further characterised by spectroscopy techniques (thin layer chromatography and ultra-high performance liquid chromatography-mass spectrometry). The antioxidant assays (both DPPH and ABTS) revealed that manghaslin exhibited better 50% inhibitory activity than ascorbic acid. Therefore, the radical scavenging activities of manghaslin are found better than clitorin, despite both being identified in the leaf juice. Bioactivity associated with the difference of their antioxidant activities shall be studied as well.

A preclinical study of a new derivative of xanthine angipur (3-methyl-8-piperiazinyl-7-thietanyl-1-ethylpurinedione hydrochloride) was carried out. In studies on the effect on the functional activity of platelets in vivo, with a single intravenous administration to rats, the studied compound significantly inhibited platelet aggregation and was comparable in terms of antiplatelet activity with the comparison drug tirofiban (ED₅₀ 0.89 vs. 0.9 mg/kg, respectively). When studying the antithrombotic effect, it was found that angipur on models of carotid artery thrombosis induced by ferric (III) chloride and electric current was also comparable to tirofiban. In conditions of generalized epinephrine-collagen thrombosis in mice, the angipur contributed to 80% survival of experimental animals and exceeded the antithrombotic activity of the comparison drug by 1.2 times. In the group of animals with experimental myocardial infarction, it was recorded that the level of antithrombotic activity of angipur was 1.7 times higher than that of tirofiban. The study of the mechanism of the antiplatelet effect of angipur by flow cytometry and ELISA, as well as under conditions of platelet stimulation by various agonists, allowed us to conclude that this agent has a blocking effect on glycoprotein IIb/IIIa platelet receptors. The study of the effect on the bleeding time allowed us to conclude that with a single intravenous injection, angipur contributed to the prolongation of the studied indicator, but to a lesser extent than the comparison drug. The therapeutic index, as the LD₅₀/ED₅₀ ratio, for angipur was 35.5, which is 6.3 times higher than the values of tirofiban. This parameter indicates a higher level of safety of angipur compared to the reference. Based on the conducted preclinical studies, taking into account the data on the study of chronic toxicity and pharmacokinetics, the starting dose for phase I clinical trials was established. Currently, phases I and II of clinical trials have been successfully completed.

Cyclic carbonates play a crucial and multifaceted role in the pharmaceutical industry due to their versatile properties and applications. They are essential intermediates in synthesizing various pharmaceutical compounds, making them indispensable in drug development. With an increasing focus on sustainable and environmentally friendly practices in the pharmaceutical sector, cyclic carbonates offer a greener alternative. They can be produced using more cycloaddition reactions of carbon dioxide to substitute epoxides, which represents an eco-friendly and economically viable procedure to form cyclic carbonates compared to traditional chemical processes, aligning with the industry’s sustainability goals.

This study investigates the development of a green and efficient catalytic process for synthesizing carbonates as pharmaceutical intermediates using carbon dioxide as a reagent. The heterogeneous catalyst employed in this research was designed and synthesized based on its environmentally benign characteristics, cost-effectiveness, and catalytic efficiency. This catalyst’s utilization minimizes the reaction's environmental impact and enhances the selectivity and yield of the interested products. The reaction mechanism and kinetics are elucidated to gain insight into the catalytic process. Furthermore, the production of cyclic carbonates as pharmaceutical precursors underscores its significance in synthesizing various drugs, providing a sustainable alternative to conventional methods.

This study highlights the importance of green chemistry principles in synthesizing valuable compounds like carbonates. Combining a heterogeneous catalyst with carbon dioxide as a renewable and abundant resource demonstrates the potential for sustainable chemical processes in the pharmaceutical industry.

Pyocyanin (PYO) is a green blue pigment that is produced extracellularly by the Gram-negative bacteria Pseudomonas aeruginosa. Its color depends on pH value. It exists in blue zwitterion form at neutral and alkaline conditions, while in an acidic environment, it becomes pink after protonation. PYO has shown the antibacterial activity, as well as the ability to inhibit the growth of fungi like Aspergillus fumigatus and Candida albicans. Moreover, it shows the high cytotoxic effect against the human pancreatic cancer cells by inducing their apoptosis. To evaluate the possible mechanism of biological activity of PYO, in the present study, we have investigated its interactions with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) by fluorescence emission spectroscopy. The obtained value of binding constant to BSA is relatively high (K_A = 5.3 × 10⁶ M^-1s^-1), showing the ability of PYO to bind to this transport protein. We have also used synchronous fluorescence spectroscopy to explore the structural changes in BSA in the presence of the studied biopigment. In contrast with the mentioned results for binding to BSA, PYO has shown a low affinity to ct-DNA, what can be seen from the value of its binding constast (K_A = 7.8 × 10³ M^-1s^-1).

The study aimed to synthesize, purify, and investigate the interaction of oligonucleotides (OLNs) with recombinant signaling proteins and their receptors, assessing the binding strength using fluorescence analysis and the Stern-Volmer equation. OLN-1 to OLN-8 were synthesized and purified, and their purity confirmed by HPLC. Fluorometric titration revealed static binding of OLNs to proteins, forming non-fluorescent complexes, except for OLN-3 with insulin (INS) and OLN-2 with interferon α2-β (INF α2-β), showing mixed binding. This indicates that these proteins interacted with OLNs at very low concentrations. OLN-1, OLN-6, OLN-7, and OLN-8 exhibited high binding activity to all proteins. Moreover, positive cooperative binding (2A+B=A2B) was observed in some cases, where one OLN molecule facilitated the attachment of the next due to conformational changes. OLN-3 and OLN-4 displayed significant positive cooperative binding with INF α2-β. In conclusion, the study demonstrated a strong interaction between OLNs and recombinant signaling proteins and receptors, potentially influencing their conformation and biological activity. These findings have implications for the therapeutic use of OLNs in the context of signaling proteins and receptors.

Since the clinical success of cisplatin, there is a growing demand for cytotoxic metal complexes able to overcome the limitations associated with cisplatin therapy. It has been extensively demonstrated that its cytotoxic activity is due to interaction with DNA. In fact, cisplatin interferes with DNA replication and transcription processes, kinking the DNA duplex by covalently binding two adjacent guanines in the major groove. Unfortunately, the use of cisplatin is associated with undesirable side effects. Therefore, a second generation of Pt-based complexes (oxaliplatin, carboplatin), and a series of non-Pt-based complexes, with different mechanisms of action, have been developed. In this frame, dirhodium tetracarboxylates, especially dirhodium tetraacetate [Rh₂(μ-O₂CCH₃)₄], attracted great interest. The paddlewheel dirhodium tetraacetate complex has been considered a potential anticancer compound since it exhibits an appreciable carcinostatic activity. Information on the interaction of this metallodrug with DNA are limited. To obtain insights on its mechanism of action, X-ray crystallography and mass spectrometry have been carried out. The X-ray structure of the dirhodium/DNA adduct reveals a bimetallic center bound to an adenine via axial coordination. This result is significant since dirhodium mode of binding to DNA is different from that of cisplatin, which binds guanines. This view is supported by ESI MS experiments, pointing out that, at short incubation times, adducts are formed between the DNA and [Rh₂(μ-O₂CCH₃)₄] in agreement with crystallographic results. Furthermore, for longer incubation times, the dirhodium tetraacetate converts into a mono-rhodium tetraacetate fragment as the consequence of progressive cleavage of the Rh-Rh bond.

Earlier in our laboratory, amide derivatives of octahydrochromene were obtained by a three-component Prince-Ritter reaction. These compounds exhibited inhibiting activity against the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1) in the low micromolar range [1]. Based on molecular modeling results, it was proposed that acetamide derivatives of octahydrochromene 3, which contain an arylpiperazine moiety, may exhibit inhibitory activity against Tdp1.

The purpose of this work is the synthesis of chiral acetamide derivatives of octahydrochromene with an arylpiperazine moiety, starting from 2-chloroacetamide, p-tolyloctahydrochromene 1, and substituted arylpiperazines 2.

The alkylation reaction was carried out in acetonitrile by boiling in the presence of К₂СО₃, after purification by column chromatography the yields of the target compounds ranged from 11 to 89%.

Compound 3а didn’t exhibit inhibitory activity against Tdp1, (IC₅₀ > 50µM), while compounds 3b-d showed inhibitory activity ranged from 19.3 to 10.3 µÐœ.

Chronic wounds represent a major problem for healthcare worldwide. Currently, the treatments used (conventional dressings) do not provide the necessary response, and new wound management approaches and innovations in dressings are needed. One of the biggest challenges in the healing of chronic wounds is the control and inhibition of microbial proliferation, keeping the wound site as sterile as possible, and hence facilitate tissue renewal. Natural extracts such as geraniol, cinnamaldehyde and citral were tested as antifungal allies, targeting Candida spp. fungi, which are often neglected in chronic wound healing. They were loaded onto polyvinyl alcohol (PVA) electrospun mats, which were also modified with halochromic molecules, namely anthocyanins. These specialized molecules can assist with the monitoring of the healing progression through pH-sensitivity, without requiring frequent dressing removal, thus preventing the destruction of newly formed tissue. Anthocyanins were obtained through in house extraction and commercially and their halochromic response verified. Antifungal natural extracts were combined with the PVA via blending (prior to electrospinning). On its turn, immobilization of anthocyanins was done also via blending or via absorption (after electrospinning and crosslinking process). The first option was found the most impactful, evidencing immediate and lasting effects of the halochromic properties, which mapped the antifungal extracts activity against the Candida spp.

Multidrug-resistant (MDR) pathogens are severely impacting our ability to successfully treat common infections. As a consequence, bacterial resistance to antimicrobial drugs represents one of the most impelling topics in medicinal chemistry. In recent years we have focused our efforts on the investigation of a panel of adarotene-related synthetic retinoids showing, together with favorable MICs, a detectable bactericidal effect on S. aureus and E. faecalis (including some MDR strains).¹ Based on these promising results, a small collection of adarotene related retinoids was prepared. Chemical modifications were performed on the carboxylic group and the double bond of the cinnamic portion, as well as polar substituents were introduced on ring A and ring B, in order to evaluate the potential structural determinants necessary to exert antibiotic activity (Figure 1). Overall, the results showed that compounds with a very good activity profile can be obtained by modulating the pattern of substitution on the adarotene moiety. Moreover, the shape and geometry of the molecules, together with the presence of key polar groups on the biphenyl backbone, could play a major role for the antimicrobial effect on resistant strains.

Figure 1: Structure of adarotene and suitable modifications on its scaffold.

The consumption of diatomaceous earth (DE) as a food supplement has healthy effects such as detoxifying the body, controlling parasites or improving joint and bone health. However, its effects on intestinal health have not been demonstrated. The aim of this study was to analyze the adaptive morphology changes at the intestinal level derived from the consumption of DE (Vitality Gesf SL) in rats. Animals were treated daily by oral gavage for one week without (C, control group) or with DE (2 mg/kg b.w) (DE group). The villi absorption area, the renewal and differentiation of the epithelium and the integrity of the barrier of the small and large intestine have been studied. DE-supplemented group showed similar results to C group with respect to villi width, crypt depth, and occludin, and the number of PAS goblet cells along the intestinal tract. As an adaptive response to DE, there was an increase in the villi area and absorption surface due to the higher index of cell proliferation in the duodenum and ileum. Furthermore, the percentage of AB goblet cells increased in the crypts of jejunum, ileum and proximal colon, improving the acidic mucus layer of the mucosa. The number of intraepithelial lymphocytes was in healthy range values, although, in all sections of the intestine, DE rats showed a tendency to increase, improving the defense system. No DE-induced negative effects have been found. DE consumption may be recommended to improve intestinal health by increasing the absorption area and maintaining the integrity of the intestinal mucosal barrier.