A Review on the Antimicrobial Activity of Schiff Bases: Data Collection and Recent Studies

Schiff bases (SBs) have extensive applications in different fields such as analytical, inor‐ ganic and organic chemistry. They are used as dyes, catalysts, polymer stabilizers, luminescence chemosensors, catalyzers in the fixation of CO2 biolubricant additives and have been suggested for solar energy applications as well. Further, a wide range of pharmacological and biological applica‐ tions, such as antimalarial, antiproliferative, analgesic, anti‐inflammatory, antiviral, antipyretic, an‐ tibacterial and antifungal uses, emphasize the need for SB synthesis. Several SBs conjugated with chitosan have been studied in order to enhance the antibacterial activity of chitosan. Moreover, the use of the nanoparticles of SBs may improve their antimicrobial effects. Herein, we provide an ana‐ lytical overview of the antibacterial and antifungal properties of SBs and chitosan‐based SBs as well as SBs‐functionalized nanoparticles. The most relevant and recent literature was reviewed for this purpose

A Look at the Importance of Chirality in Drug Activity: Some Significative Examples

[EN] Chirality plays an important role in the development of many pharmaceuticals, being a general property of 'handedness'; nevertheless, a large number of pharmaceuticals are still marketed and administered as racemates. Chirality is all around and even within us; indeed, receptors and enzymes are chiral entities and interact in a specific manner with chiral drugs. Consequently, controlling enantiomeric purity and isolating the enantiomers from chiral drugs remains a crucial subject for analytical, clinical, and regulatory purposes, thus, improving the drug safety profile. The classical examples of spontaneous enantiomerization and severe toxicity related to chirality are represented by ibuprofen and thalidomide, respectively, but numerous other cases have been reported in the literature. This review intends to offer a brief overview on the most common chiral drugs used in therapy for the treatment of various diseases.Ceramella, J.; Iacopetta, D.; Franchini, A.; De Luca, M.; Saturnino, C.; Andreu, I.; Sinicropi, MS.... (2022). A Look at the Importance of Chirality in Drug Activity: Some Significative Examples. Applied Sciences. 12(21):1-22. https://doi.org/10.3390/app122110909122122

Target Therapy in Cancer Treatment: mPGES-1 and PARP

Target therapy is an approach focusing on specific protein or signaling pathways. This therapy is directly aimed to a molecular target such as a receptor, growth factor or enzyme in cancer cells. These targets are used by the tumor cells themselves to obtain uncontrolled proliferation, resistance to traditional therapies and to increase the number of blood vessels in the tissue of origin (neoangiogenesis). A purpose of target therapy may be to counteract the growth and proliferation of cancer cells through the use of drugs or monoclonal antibodies capable of inhibiting the receptor for the epidermal growth factor (EGFR), that is crucial in the process of neo-angiogenesis, protein kinases (PKs), as regulators of cell growth signals and human epidermal growth factor type 2 (HER2), which is essential in stimulating growth and proliferation of cancer cells. Among anticancer drugs, Bevacizumab, a humanised monoclonal antibody produced by recombinant DNA technique, is used for the first-line treatment of metastatic breast cancer, as it inhibits EGFR and the vascular endothelial cell growth factor (VEGF). Abemaciclib, a protein kinase inhibitor drug, is also used for the treatment of the same cancer. In 20-30% of primary breast tumors, the excessive expression of HER2 is observed; thus, HER2 inhibitors may represent another plausible therapy. A potent HER2 inhibitor is the recombinant humanized igG1 monoclonal antibody Trastuzumab, which was first tested in 1992 and is currently used for the treatment of HER2 positive breast cancer. Unfortunately, despite the numerous advances in finding new therapies, patients treated with these drugs often suffer from severe undesirable side effects. Therefore, the search for new therapeutic targets may be desirable. In this paper we analyse particularly two targets studied quite recently: the microsomal prostaglandin E2 synthase type 1 (mPGES-1) and poly (ADP-ribose) polymerase (PARP) proteins

Benzothiazole-Containing Analogues of Triclocarban with Potent Antibacterial Activity

Triclocarban (TCC) is a polychlorinated, aromatic, antimicrobial agent commercially used since the 1950s in personal care products for the prevention of spoilage and infections. Humans are frequently exposed to TCC due to its widespread use, leading to its substantial release into the aquatic environment. With the recent ban of TCC from some personal care products, implemented in 2016, many replacement antimicrobial compounds have been studied by researchers. Herein, we report the synthesis and biological activity of a series of diarylureas, analogues of TCC that bear the benzothiazole nucleus as one of the two aryl moieties. Among the studied compounds, 2bF and 2eC showed the highest antimicrobial activity against Staphylococcus aureus, being also more active than TCC, with MIC values of 8 µg/mL versus 16 µg/mL of TCC. Moreover, compound 2bB was much more active than TCC against Enterococcus faecalis, a Gram-positive bacterium that is, unfortunately, strongly responsible for nosocomial infections. Finally, interesting results were found for compound 2bG that, even though less active than the others, exerts an interesting bactericidal action

Target Therapy in Cancer Treatment: mPGES-1 and PARP

Target therapy is an approach focusing on specific protein or signaling pathways. This therapy is directly aimed to a molecular target such as a receptor, growth factor or enzyme in cancer cells. These targets are used by the tumor cells themselves to obtain uncontrolled proliferation, resistance to traditional therapies and to increase the number of blood vessels in the tissue of origin (neoangiogenesis). A purpose of target therapy may be to counteract the growth and proliferation of cancer cells through the use of drugs or monoclonal antibodies capable of inhibiting the receptor for the epidermal growth factor (EGFR), that is crucial in the process of neo-angiogenesis, protein kinases (PKs), as regulators of cell growth signals and human epidermal growth factor type 2 (HER2), which is essential in stimulating growth and proliferation of cancer cells. Among anticancer drugs, Bevacizumab, a humanised monoclonal antibody produced by recombinant DNA technique, is used for the first-line treatment of metastatic breast cancer, as it inhibits EGFR and the vascular endothelial cell growth factor (VEGF). Abemaciclib, a protein kinase inhibitor drug, is also used for the treatment of the same cancer. In 20-30% of primary breast tumors, the excessive expression of HER2 is observed; thus, HER2 inhibitors may represent another plausible therapy. A potent HER2 inhibitor is the recombinant humanized igG1 monoclonal antibody Trastuzumab, which was first tested in 1992 and is currently used for the treatment of HER2 positive breast cancer. Unfortunately, despite the numerous advances in finding new therapies, patients treated with these drugs often suffer from severe undesirable side effects. Therefore, the search for new therapeutic targets may be desirable. In this paper we analyse particularly two targets studied quite recently: the microsomal prostaglandin E2 synthase type 1 (mPGES-1) and poly (ADP-ribose) polymerase (PARP) proteins

COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of the Coronavirus family which caused the worldwide pandemic of human respiratory illness coronavirus disease 2019 (COVID-19). Presumably emerging at the end of 2019, it poses a severe threat to public health and safety, with a high incidence of transmission, predominately through aerosols and/or direct contact with infected surfaces. In 2020, the search for vaccines began, leading to the obtaining of, to date, about twenty COVID-19 vaccines approved for use in at least one country. However, COVID-19 continues to spread and new genetic mutations and variants have been discovered, requiring pharmacological treatments. The most common therapies for COVID-19 are represented by antiviral and antimalarial agents, antibiotics, immunomodulators, angiotensin II receptor blockers, bradykinin B2 receptor antagonists and corticosteroids. In addition, nutraceuticals, vitamins D and C, omega-3 fatty acids and probiotics are under study. Finally, drug repositioning, which concerns the investigation of existing drugs for new therapeutic target indications, has been widely proposed in the literature for COVID-19 therapies. Considering the importance of this ongoing global public health emergency, this review aims to offer a synthetic up-to-date overview regarding diagnoses, variants and vaccines for COVID-19, with particular attention paid to the adopted treatments

Diarylureas: New Promising Small Molecules against Streptococcus mutans for the Treatment of Dental Caries

Dental caries is a biofilm-mediated disease that represents a worldwide oral health issue. Streptococcus mutans has been ascertained as the main cariogenic pathogen responsible for human dental caries, with a high ability to form biofilms, regulated by the quorum sensing. Diarylureas represent a class of organic compounds that show numerous biological activities, including the antimicrobial one. Two small molecules belonging to this class, specifically to diphenylureas, BPU (1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea) and DMTU (1,3-di-m-tolyl-urea), showed interesting results in studies regarding the antimicrobial activity against the cariogenic bacterium S. mutans. Since there are not many antimicrobials used for the prevention and treatment of caries, further studies on these two interesting compounds and other diarylureas against S. mutans may be useful to design new effective agents for the treatment of caries with generally low cytotoxicit

Impact of Cytochrome P450 Enzymes on the Phase I Metabolism of Drugs

The cytochrome P450 (CYP) enzyme family is the major enzyme system catalyzing the phase I metabolism of xenobiotics, including pharmaceuticals and toxic compounds in the environment. A major part of the CYP-dependent xenobiotic metabolism is due to polymorphic and inducible enzymes, which may, quantitatively or qualitatively, alter or enhance drug metabolism and toxicity. Drug–drug interactions are major mechanisms caused by the inhibition and/or induction of CYP enzymes. Particularly, CYP monooxygenases catalyze hydroxylation reactions to form hydroxylated metabolites. The secondary metabolites are sometimes as active as the parent compound, or even more active. The aim of this review is to summarize some of the significative examples of common drugs used for the treatment of diverse diseases and underline the activity and/or toxicity of their metabolites

NUTRACEUTICAL FUNCTIONS OF GREEN TEA

Today, the diffusion of neoplastic diseases is a widespread phenomenon. Thus, it is always necessary to identify new molecules able to fight them. In this paper, we will deal with the interesting antineoplastic properties of green tea. We will describe the different and plausible anticancer mechanisms of epigallocatechin gallate (EGCG), the major polyphenol found in green tea, and in particular the biochemical and computational discovery of a new target for the treatment of this disease will be discussed. The bio-active substances present in tea are essentially represented by methylxanthines, as well as by the antioxidant phenolic fraction (flavonoids). Among the other active substances contained in lower concentrations there are vitamins (B, C and K), amino acids (L-theanine) and minerals (aluminium and manganese). Tea extracts, particularly EGCG, could represent the starting point for the potential emergence of new drugs for the treatment of neoplastic diseases. Other activities of tea, as the involvement in neurodegenerative diseases prevention, as well as the antioxidant, antibacterial, antifungal and antiviral effects, will be also briefly described

NUTRACEUTICAL FUNCTIONS OF GREEN TEA

Today, the diffusion of neoplastic diseases is a widespread phenomenon. Thus, it is always necessary to identify new molecules able to fight them. In this paper, we will deal with the interesting antineoplastic properties of green tea. We will describe the different and plausible anticancer mechanisms of epigallocatechin gallate (EGCG), the major polyphenol found in green tea, and in particular the biochemical and computational discovery of a new target for the treatment of this disease will be discussed. The bio-active substances present in tea are essentially represented by methylxanthines, as well as by the antioxidant phenolic fraction (flavonoids). Among the other active substances contained in lower concentrations there are vitamins (B, C and K), amino acids (L-theanine) and minerals (aluminium and manganese). Tea extracts, particularly EGCG, could represent the starting point for the potential emergence of new drugs for the treatment of neoplastic diseases. Other activities of tea, as the involvement in neurodegenerative diseases prevention, as well as the antioxidant, antibacterial, antifungal and antiviral effects, will be also briefly described