132 research outputs found
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
Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation
Sericin is a natural protein that has been used in biomedical and pharmaceutical fields as raw material for polypeptide-based drug delivery systems (DDSs). In this paper, it has been employed as pharmaceutical biopolymer for the production of sunitinib–polypeptide conjugate. The synthesis has been carried out by simple click reaction in water, using the redox couple l-ascorbic acid/hydrogen peroxide as a free radical grafting initiator. The bioconjugate molecular weight (50 kDa < Mw < 75 kDa) was obtained by SDS-PAGE, while the spectroscopic characteristics have been studied in order to reveal the presence of grafted sunitinib. In both FT-IR and UV/Vis spectra, signals corresponding to sunitinib functional groups have been identified. Since sunitinib is an anticancer drug characterized by low bioavailability and low permeability, the bioconjugation aimed at their enhancement. In vitro studies demonstrated that bioavailability has been increased to almost 74%, compared with commercial formulation. Also cell membrane permeability has been augmented in in vitro tests, in which membrane models have been used to determine the lipid membrane/physiological fluid partition coefficient (Kp). The log(Kp) value of the bioconjugate was increased to over 4. This effect resulted in a three-fold decrease of IC50 value against MCF-7 cells
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
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
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
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
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
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
Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment
Over the past decade, metal complexes based on N-heterocyclic carbenes (NHCs) have
attracted great attention due to their wide and exciting applications in material sciences and medicinal
chemistry. In particular, the gold-based complexes are the focus of research efforts for the development of new anticancer compounds. Literature data and recent results, obtained by our research group, reported the design, the synthesis and the good anticancer activity of some silver and gold complexes
with NHC ligands. In particular, some of these complexes were active towards some breast cancer cell lines. Considering this evidence, here we report some new Au-NHC complexes prepared in order to improve solubility and biological activity. Among them, the compounds 1 and 6 showed an interesting anticancer activity towards the breast cancer MDA-MB-231 and MCF-7 cell lines, respectively. In addition, in vitro and in silico studies demonstrated that they were able to inhibit the activity of the human topoisomerases I and II and the actin polymerization reaction. Moreover, a downregulation of vimentin expression and a reduced translocation of NF-kB into the nucleus was observed. The interference with these vital cell structures induced breast cancer cells’ death by triggering the extrinsic apoptotic pathway
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