Formulation, development and evaluation of hyaluronic acid-conjugated liposomal nanoparticles loaded with regorafenib and curcumin and their in vitro evaluation on colorectal cancer cell lines.

Colorectal cancer is one of the major causes of global cancer, with chemotherapy and radiation therapy being effective but limited due to low specificity. Regorafenib, a multikinase inhibitor, provides hope to patients with metastatic colorectal cancer and was approved by the FDA in 2012. However, due to resistance issues and adverse events, its efficacy is compromised, necessitating further refinement. Meanwhile, curcumin, a compound of turmeric, exhibits anticancer effects through antioxidant and anti-inflammatory actions, induction of the apoptosis, arrest of cell cycle, inhibition of angiogenesis, and modulation of signaling pathways. Unfortunately, its clinical utility is limited by its poor bioavailability, pointing towards innovative drug delivery strategies for enhanced efficacy in colorectal cancer treatment. Hyaluronic acid (HA)-decorated liposomes (LIPO) have been developed to target colorectal cells through an overexpressed CD44 receptor, increasing antitumor and antimetastasis efficacy. This study investigates the possibility of loading curcumin (CUR) or regorafenib (REGO) into a liposomal formulation for passive and HA-actively targeted treatment, evaluating its critical quality attributes (CQA) (size, zeta potential, polydispersity index) and cytotoxic activity in the HT29 colorectal cancer cell line. The average particle size of the plain liposomes and those decorated with HA was 144.00 ± 0.78 nm and 140.77 ± 1.64 nm, respectively. In contrast, curcumin-loaded plain liposomes and HA-decorated liposomes had 140 ± 2.46 nm and 164.53 ± 15.13 nm, respectively. The prepared liposomes had a spherical shape with a narrow size distribution and an acceptable zeta potential of less than -30 mV. The encapsulation efficiency was 99.2 % ± 0.3 and 99.9 ± 0.2 % for HA-decorated and bare regorafenib loaded. The % EE was 98.9 ± 0.2 % and 97.5 ± 0.2 % for bare liposomal nanoparticles loaded with curcumin and coated with curcumin. The IC50 of free REGO, CUR, REGO-LIPO, CUR-LIPO, REGO-LIPO-HA and CUR-LIPO-HA were 20.17 ± 0.78, 64.4 ± 0.33, 224.8 ± 0.06, 49.66 ± 0.22, 73.66 ± 0.6, and 27.86 ± 0.49 µM, respectively. The MTT assay in HT29 cells showed significant cytotoxic activity of the HA-decorated liposomal formulation compared to the base uncoated formulation, indicating that hyaluronic acid-targeted liposomes loaded with regorafenib or curcumin could be a promising targeted formulation against colorectal cancer cells.

Novel Matrix Metalloproteinase-9 (MMP-9) Inhibitors in Cancer Treatment.

Matrix metalloproteinases (MMPs) belong to a family of zinc-dependent proteolytic metalloenzymes. MMP-9, a member of the gelatinase B family, is characterized as one of the most intricate MMPs. The crucial involvement of MMP-9 in extracellular matrix (ECM) remodeling underscores its significant correlation with each stage of cancer pathogenesis and progression. The design and synthesis of MMP-9 inhibitors is a potentially attractive research area. Unfortunately, to date, there is no effective MMP-9 inhibitor that passes the clinical trials and is approved by the FDA. This review primarily focuses on exploring the diverse strategies employed in the design and advancement of MMP-9 inhibitors, along with their anticancer effects and selectivity. To illuminate the essential structural characteristics necessary for the future design of novel MMP-9 inhibitors, the current narrative review highlights several recently discovered MMP-9 inhibitors exhibiting notable selectivity and potency.

Matrix Metalloproteinases Inhibitors in Cancer Treatment: An Updated Review (2013-2023).

Matrix metalloproteinases (MMPs) are identifiable members of proteolytic enzymes that can degrade a wide range of proteins in the extracellular matrix (ECM). MMPs can be categorized into six groups based on their substrate specificity and structural differences: collagenases, gelatinases, stromelysins, matrilysins, metalloelastase, and membrane-type MMPs. MMPs have been linked to a wide variety of biological processes, such as cell transformation and carcinogenesis. Over time, MMPs have been evaluated for their role in cancer progression, migration, and metastasis. Accordingly, various MMPs have become attractive therapeutic targets for anticancer drug development. The first generations of broad-spectrum MMP inhibitors displayed effective inhibitory activities but failed in clinical trials due to poor selectivity. Thanks to the evolution of X-ray crystallography, NMR analysis, and homology modeling studies, it has been possible to characterize the active sites of various MMPs and, consequently, to develop more selective, second-generation MMP inhibitors. In this review, we summarize the computational and synthesis approaches used in the development of MMP inhibitors and their evaluation as potential anticancer agents.

Synthesis, Characterization and Nanoformulation of Novel Sulfonamide-1,2,3-triazole Molecular Conjugates as Potent Antiparasitic Agents.

Toxoplasma gondii (T. gondii) is a highly prevalent parasite that has no gold standard treatment due to the poor action or the numerous side effects. Focused sulfonamide-1,2,3-triazole hybrids 3a-c were wisely designed and synthesized via copper catalyzed 1,3-dipolar cycloaddition approach between prop-2-yn-1-alcohol 1 and sulfa drug azides 2a-c. The newly synthesized click products were fully characterized using different spectroscopic experiments and were loaded onto chitosan nanoparticles to form novel nanoformulations for further anti-Toxoplasma investigation. The current study proved the anti-Toxoplasma effectiveness of all examined compounds in experimentally infected mice. Relative to sulfadiazine, the synthesized sulfonamide-1,2,3-triazole (3c) nanoformulae demonstrated the most promising result for toxoplasmosis treatment as it resulted in 100% survival, 100% parasite reduction along with the remarkable histopathological improvement in all the studied organs.

Data privacy and confidentiality from the perspectives of general public and health care providers in Jordan.

OBJECTIVES: To assess knowledge, attitude, and beliefs about the right to privacy and confidentiality from the viewpoints of the general public (GP) and the health system (HS) professionals in Jordan. METHODS: An online-based cross-sectional descriptive questionnaire was distributed across Jordan during May & June of 2020. A total number of 388 respondents filled in the online survey assessing their knowledge, attitude, and opinion about the right to privacy and confidentiality being practiced during the professional contact between the patients and their health care providers. RESULTS: Amongst the respondents, 44 (11.3%) participants were health care professionals, and 344 (88.6%) participants were from the general public. Most of the respondents were females (69.6%) and the mean age was about 27 years. The main sources of knowledge about patients' right to privacy and confidentiality regulations were from school and media platforms. Only 18.1% of the GP respondents reported that they have been introduced to patients' right to privacy and confidentiality regulations by medical staff during professional contact. Almost about 97% of GP respondents and 93.2% of HS professionals valued patients' right to assure the level of their data privacy prior to receiving medical care. A significantly (P = .012) higher percentage (93%) of GP respondents believed that there should be no prioritisation of privacy based on the gender of the patient. Most of the GP respondents had concerns about electronic medical records being violated and their data being reached by unauthorised parties. CONCLUSION: The general public and health system professionals in Jordan are familiar with the patients' right to privacy and confidentiality regulations. More efforts must be put in place to inform patients about their rights to privacy and confidentiality practices when they are in professional contact with their healthcare providers. In addition, rules, laws, and legal agreements must be effectively established and monitored to prevent privacy violations.

Novel Dipyridinium Lipophile-Based Ionic Liquids Tethering Hydrazone Linkage: Design, Synthesis and Antitumorigenic Study.

Novel dicationic pyridinium ionic liquids tethering amphiphilic long alkyl side chains and fluorinated counter anions have been successfully synthesized by means of the quaternization of the dipyridinium hydrazone through its alkylation with different alkyl halides. The resulting halogenated di-ionic liquids underwent a metathesis reaction in order to incorporate some fluorinated counter anions in their structures. The structures of all the resulting di-ionic liquids were characterized by several spectroscopic experiments. The antitumorigenic activities of the investigated compounds were further studied against three different human lung cancer cell lines. Compared to the standard chemotherapeutic agent, cisplatin, the synthesized di-ionic liquids exerted equal, even more active, moderate, or weak anticancer activities against the various lung cancer cell lines under investigation. The observed anticancer activity appears to be enhanced by increasing the length of the aliphatic side chains. Moreover, dicationic pyridinium bearing a nine carbon chain as counter cation and hexafluoro phosphate and/or tetrafluoro bororate as counter anion were selected for further evaluation and demonstrated effective and significant antimetastatic effects and suppressed the colonization ability of the lung cancer cells, suggesting a therapeutic potential for the synthesized compounds in lung cancer treatment.

Monoamine Oxidase (MAO) as a Potential Target for Anticancer Drug Design and Development.

Monoamine oxidases (MAOs) are oxidative enzymes that catalyze the conversion of biogenic amines into their corresponding aldehydes and ketones through oxidative deamination. Owing to the crucial role of MAOs in maintaining functional levels of neurotransmitters, the implications of its distorted activity have been associated with numerous neurological diseases. Recently, an unanticipated role of MAOs in tumor progression and metastasis has been reported. The chemical inhibition of MAOs might be a valuable therapeutic approach for cancer treatment. In this review, we reported computational approaches exploited in the design and development of selective MAO inhibitors accompanied by their biological activities. Additionally, we generated a pharmacophore model for MAO-A active inhibitors to identify the structural motifs to invoke an activity.

Encapsulation of ionic liquids inside cucurbiturils.

Cucurbit[n]urils (CBn, n = 6-8) serve as molecular receptors for imidazolium-based ionic liquids (ILs) in aqueous solution. The amphiphilic nature of 1-alkyl-3-methylimidazolium guests (Cnmim), with a cationic imidazolium residue and a hydrophobic alkyl chain, enabled their complexation with CBn through a combination of the hydrophobic effect and ion-dipole interactions. 1H NMR experiments revealed that the cavity of CBn can host the hydrophobic chain of the ILs, while one of the carbonyl rims served as a docking site for the imidazolium ring. The structure of the complexes was further analyzed by molecular dynamics (MD) simulations, which indicated that the cavity of CB6 can accommodate up to 5 carbon atoms, while the larger cavity of CB7 and CB8 can encapsulate longer alkyl chains in folded conformations. Isothermal titration calorimetry (ITC) experiments provided up to micromolar affinity of ILs to CBn in aqueous solution, which was independently quantified by indicator displacement titrations.

Synthesis and evaluation of 2,4,5-trisubstitutedthiazoles as carbonic anhydrase-III inhibitors.

A series of 17 compounds (12-16 b) with 2,4,5-trisubstitutedthiazole scaffold having 5-aryl group, 4-carboxylic acid/ester moiety, and 2-amino/amido/ureido functional groups were synthesised, characterised, and evaluated for their carbonic anhydrase (CA)-III inhibitory activities using the size exclusion Hummel-Dreyer method (HDM) of chromatography. Compound 12a with a free amino group at the 2-position, carboxylic acid moiety at the 4-position, and a phenyl ring at the 5-position of the scaffold was found to be the most potent CA-III inhibitor (Ki = 0.5 µM). The presence of a carboxylic acid group at the 4-position of the scaffold was found to be crucial for the CA-III inhibitory activity. Furthermore, replacement of the free amino group with an amide and urea group resulted in a significant reduction of activity (compounds 13c and 14c, Ki = 174.1 and 186.2 µM, respectively). Thus, compound 12a (2-amino-5-phenylthiazole-4-carboxylic acid) can be considered as the lead molecule for further modification and development of more potent CA-III inhibitors.

N-Phenyl-6-Chloro-4-Hydroxy-2-Quinolone-3-CarboxAmides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents.

Cancer is a multifactorial disease and the second leading cause of death worldwide. Diverse factors induce carcinogenesis, such as diet, smoking, radiation, and genetic defects. The phosphatidylinositol 3-kinase (PI3Kα) has emerged as an attractive target for anticancer drug design. Eighteen derivatives of N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamide were synthesized and characterized using FT-IR, NMR (1H and 13C), and high-resolution mass spectra (HRMS). The series exhibited distinct antiproliferative activity (IC50 µM) against human epithelial colorectal adenocarcinoma (Caco-2) and colon carcinoma (HCT-116) cell lines, respectively: compounds 16 (37.4, 8.9 µM), 18 (50.9, 3.3 µM), 19 (17.0, 5.3 µM), and 21 (18.9, 4.9 µM). The induced-fit docking (IFD) studies against PI3Kαs showed that the derivatives occupy the PI3Kα binding site and engage with key binding residues.

Chemical Composition, Antioxidant, Anti-Tyrosinase, Anti-Cholinesterase and Cytotoxic Activities of Essential Oils of Six Algerian Plants.

In this study, the essential oils (EOs) of six Algerian plants (Artemisia campestris L., Artemisia herba-alba Asso, Juniperus phoenicea L., Juniperus oxycedrus L., Mentha pulegium L. and Lavandula officinalis Chaix) were obtained by hydrodistillation, and their compositions determined by GC-MS and GC-FID. The antioxidant activity of the EOS was evaluated via 2,2'-diphenyl-1-picrylhydrazyl (DPPH), ferric-reducing/antioxidant power (FRAP) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays. Moreover, their cytotoxic effect was evaluated-as well as their tyrosinase, acetyl- and butyryl-cholinesterase (AChE and BuChE) inhibitory activities. The chemical analyses detected 44, 45, 51, 53, 26 and 40 compounds in EOs of A. campestris, A. herba-alba, J. phoenicea, J. oxycedrus, M. pulegium and L. officinalis, respectively. A. campestris EO was mainly composed of ß-pinene (20.7%), while A. herba-alba EO contained davanone D (49.5%) as the main component. α-Pinene (41.8%) was detected as the major constituent in both J. phoenicea (41.8%) and J. oxycedrus (37.8%) EOs. M. pulegium EO was characterized by pulegone as the most abundant (76.9%) compound, while linalool (35.8%) was detected as a major constituent in L. officinalis EO. The antioxidant power evaluation revealed IC50 values ranging from 2.61 to 91.25 mg/mL for DPPH scavenging activity, while the FRAP values ranged from 0.97-8.17 µmol Trolox equivalents (TX)/g sample. In the ABTS assay, the values ranged from 7.01 to 2.40 µmol TX/g sample. In the presence of 1 mg/mL of the samples, tyrosinase inhibition rates ranged from 11.35% to 39.65%, AChE inhibition rates ranged from 40.57% to 73.60% and BuChE inhibition rates ranged from 6.47% to 72.03%. A significant cytotoxic effect was found for A. herba-alba EO. The obtained results support some of the traditional uses of these species in food preservation and for protection against several diseases.

Molecular Modeling, Synthesis and Biological Evaluation of N-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer Agents.

The emergence of phosphatidylinositol 3-kinase (PI3Kα) in cancer development has accentuated its significance as a potential target for anticancer drug design. Twenty one derivatives of N-phenyl-4-hydroxy-6-methyl-2-quinolone-3-carboxamide were synthesized and characterized using NMR (1H and 13C) and HRMS. The derivatives displayed inhibitory activity against human epithelial colorectal adenocarcinoma (Caco-2) and human colon cancer (HCT-116) cell lines: compounds 8 (IC50 Caco-2 = 98 µM, IC50 HCT-116 = 337 µM) and 16 (IC50 Caco-2 = 13 µM, IC50 HCT-116 = 240.2 µM). Results showed that compound 16 significantly affected the gene encoding AKT, BAD, and PI3K. The induced-fit docking (IFD) studies against PI3Kα demonstrated that the scaffold accommodates the kinase domains and forms H-bonds with significant binding residues.

Ponicidin as a promising anticancer agent: Its biological and biopharmaceutical profile along with a molecular docking study.

Ponicidin, an ent-kaurane diterpenoid derived from Rabdosia rubescens, exhibits antitumor activities against several types of cancers. This review summarizes the botanical sources, biological activities, and biopharmaceutical profile of ponicidin. Additionally, a molecular docking study has been undertaken to correlate the interaction of this diterpenoid with biomacromolecules found in the literature. For this purpose, an up-to-date (till December 2018) literature survey was conducted using a number of databases such as PubMed, Science Direct, Web of Science, Scopus, the American Chemical Society, Clinicaltrials.gov, and Google Scholar. Findings suggest that ponicidin exerts antioxidant and anticancer activity in various test systems, including experimental animals and cultured cancer cells. Research findings revealed that anticancer mechanisms of ponicidin include antioxidant/oxidative stress induction, cytotoxic, apoptotic inductive, chemosensitizer, antiangiogenic, and antiproliferative effects. In silico study suggests that 5ITD (PI3K) was the best protein with which ponicidin interacts to exert its anticancer effect. In conclusion, ponicidin might be a promising plant-derived cancer chemotherapeutic agent.

Oral contraceptive and breast cancer: do benefits outweigh the risks? A case - control study from Jordan.

BACKGROUND: Oral contraceptives (OCs) use has been linked to increased risk of breast cancer (BC) in several reports from the world. Limited number of similar studies have been conducted in the Middle Eastern female population. This study aimed to explore any possible correlation between the contemporary and duration of OCs use among Jordanian women and the risk of breast cancer. METHODS: A case control study was conducted in 450 Jordanian women (225 as cases and 225 as controls), aged 18 to 65. Chi-square test was used to study the association between risk of breast cancer and different factors. Mann Whitney-U test was employed to evaluate the relation between time-dependent risk factor and breast cancer. RESULTS: Our results indicated that regular use of OCs exhibited association with increased risk of breast cancer (OR = 2.25, 95% CI 1.34-2.79; p = 0.002), while the duration of OCs use was not associated with the increased risk of breast cancer (p > 0.05). In addition, other factors demonstrated significant association with the increased risk of breast cancer such as age at puberty, age at menopause, previous pregnancies, menopausal status, and family history of cancer. CONCLUSIONS: regular use of OCs may be associated with increased risk of breast cancer in Jordanian women. A larger sample size in multi-center setting study is required to confirm this finding among the Jordanian female population.

Chemical composition and bioactivity of essential oils and Ethanolic extracts of Ocimum basilicum L. and Thymus algeriensis Boiss. & Reut. from the Algerian Saharan Atlas.

BACKGROUND: There is increasing interest in the pharmaceutical and food industries to substitute synthetic chemicals with naturally occurring compounds possessing bioactive properties. Plants are valuable sources of bioactive compounds. The present study investigates the chemical composition and antioxidant, antimicrobial, and anticancer activities of ethanolic extracts (EEs) and essential oils (EOs) from two species in the Lamiaceae family, Ocimum basilicum L. and Thymus algeriensis Boiss. & Reut., cultivated in the Algerian Saharan Atlas. METHODS: The total flavonoid contents of the plants' ethanolic extracts were determined by the aluminium chloride method, while the total phenols were determined using the Folin-Ciocalteu method. Essential oils were obtained by hydrodistillation of the aerial parts of the plants and were analysed by GC-MS. The free radical-scavenging ability and antioxidant potential of the plants' EEs and EOs were probed using the 2, 2-diphenyl-picrylhydrazyl radical-scavenging, ABTS radical-scavenging, ferric-reducing power and phosphomolybdenum assays. The antimicrobial activities were evaluated against several pathogens characteristic of gram-negative bacteria (three species), gram-positive bacteria (three species) and fungi (two species). The microdilution method was used to estimate the minimum inhibitory concentrations (MICs). The oils' anticancer potential against several cancer types was also studied using the MTT assay and reported as the toxic doses that resulted in a 50% reduction in cancer cell growth (LD50). RESULTS: Phenolic compounds in the EEs from both plants were analysed by HPLC and demonstrated a rich flavonoid content. Chemical analysis of the essential oil from Ocimum basilicum revealed 26 unique compounds, with linalool (52.1%) and linalyl acetate (19.1%) as the major compounds. A total of 29 compounds were identified in the essential oil from Thymus algeriensis, with α-terpinyl acetate (47.4%), neryl acetate (9.6%), and α-pinene (6.8%) as the major compounds. The ethanolic extracts and essential oils from both plants exhibited moderate antioxidant activities and moderate to weak antimicrobial activities. Furthermore, anticancer activities against the examined human cancer cell lines were associated with only the EOs from both plants, with LD50 values ranging between 300 and 1000 µg/mL. CONCLUSION: The results suggest that the bioactive compounds found in the ethanolic extracts and essential oils from Ocimum basilicum and Thymus algeriensis, with diverse antioxidant, antimicrobial and anticancer activities, may have beneficial applications in nutraceutical and pharmaceutical technologies.

Impediments to use of oral contraceptives among refugee women in camps, Jordan.

OBJECTIVES: This study aimed to assess factors related to oral contraceptive (OC) use among refugee married women in the age range 18-50 years, residing in refugee camps in Jordan. METHODS: A face-to-face questionnaire was completed by 425 women, who had used OCs at least once in their lifetime as a contraceptive method. Data were collected between November 2016 and January 2017. RESULTS: About 45 percent of women preferred OCs as a contraceptive method. Most (80 percent) women thought OCs were effective, while 68.5 percent were concerned about their safety. About 10.6 percent women became pregnant while using OCs, and 75 percent reported side effects, specifically headache (54.6 percent), irritability (46.4 percent), mood swings (39.1 percent), and weight gain (30.6 percent). However, only 21.2 percent of participating women reported that they knew how to use OCs. Alarmingly, 85.9 percent of women reported that they skipped the OC pill when they missed using it. Knowledge about correct use was directly correlated with education, number of pregnancies and children, and duration of OC use. CONCLUSION: Women residing in refugees' camps in Jordan had relative unwillingness to use OCs. Although they tended to use them appropriately and had fair experience with their use, large gaps in their knowledge were apparent.

Discovery of potent polyphosphate kinase 1 (PPK1) inhibitors using structure-based exploration of PPK1Pharmacophoric space coupled with docking analyses.

Inorganic polyphosphate (polyP) is present in all living forms of life. Studied mainly in prokaryotes, polyP and its associated enzymes are vital in diverse metabolic activities, in some structural functions, and most importantly in stress responses. Bacterial species, including many pathogens, encode a homolog of a major polyP synthesis enzyme, Poly Phosphate Kinase (PPK) with 2 different genes coding for PPK1 and PPK2. Genetic deletion of the ppk1 gene leads to reduced polyP levels and the consequent loss of virulence and stress adaptation responses. This far, no PPK1 homolog has been identified in higher-order eukaryotes, and, therefore, PPK1 represents a novel target for chemotherapy. The aim of the current study is to investigate PPK1 from Escherichia coli with comprehensive understanding of the enzyme's structure and binding sites, which were used to design pharmacophores and screen a library of compounds for potential discovery of selective PPK1 inhibitors. Verification of the resultant inhibitors activities was conducted using a combination of mutagenic and chemical biological approaches. The metabolic phenotypic maps of the wild type E. coli (WT) and ppk1 knockout mutant were generated and compared with the metabolic map of the chemically inhibited WT. In addition, biofilm formation ability was measured in WT, ppk1 knockout mutant, and the chemically inhibited WT. The results demonstrated that chemical inhibition of PPK1, with the designed inhibitors, was equivalent to gene deletion in altering specific metabolic pathways, changing the metabolic fingerprint, and suppressing the ability of E. coli to form a biofilm.

Chemical composition, antioxidant, antimicrobial and Antiproliferative activities of essential oil of Mentha spicata L. (Lamiaceae) from Algerian Saharan atlas.

BACKGROUND: Mentha spicata (M. spicata) is a member of Lamiaceae that spreads mainly in the temperate and sub-temperate zones of the world. It is considered as a rich source of essential oils, which is widely used in pharmaceutical industries and food production. The objectives of the current study were to evaluate chemical composition, antioxidant, antimicrobial and antiproliferative activities associated with the essential oil of M. spicata cultivated in Algerian Saharan Atlas. METHODS: The aerial parts of M. spicata were subjected to hydrodistillation to produce the oil. Chemical identification of the oil composition was conducted by GC and GC-MS analyses. The antioxidant activity of the hydrodistilled oil was studied using DPPH, ABTS radical scavenging and ferric-reducing power assay. Antimicrobial potential was characterized against two microorganisms, signifying Gram positive, and Gram negative bacteria, and one Candida species. The microdilution method was employed to determine the minimum inhibitory concentration (MIC). The oil's antiproliferative effects against three human tumor cell lines were also investigated using the MTT assay, and the toxic doses that yielded 50% reduction of cell viability (LD50) were reported. RESULTS: Chemical analysis of the essential oil composition revealed 44 unique compounds with oxygenated monoterpenes (67.2%), followed by monoterpene hydrocarbons (20.8%), as the most abundant chemical components. Essential oil of M. spicata demonstrated moderate antioxidant activities as well as moderate to weak antimicrobial activities with best susceptibility observed for Gram positive bacteria towards the oil. In addition, anticancer activities that are associated with the oil against three human cancer cell lines were observed with LD50 values of 324 µg/mL, 279 µg/mL, 975 µg/mL against T47D, HCT-116 and MCF-7 cell lines, respectively. CONCLUSION: The results suggest that M. spicata essential oil may have potential value as a bioactive oil, for nutraceutical and medical applications, with its antioxidant, antimicrobial and antiproliferative activities.

Phenolic Compounds and Bioactivity of Cytisus villosus Pourr.

The present study focuses on the chemical composition, antioxidant, antimicrobial, and antiproliferative activities of the ethyl acetate and aqueous extracts obtained from the aerial parts of Cytisus villosus Pourr. HPLC-DAD-ESI/MSn was used to identify the phenolic compounds, being (epi)gallocatechin dimer the major compound (111 ± 5 µg/g·dw) in the aqueous extract, while myricetin-O-rhamnoside (226 ± 9 µg/g·dw) was the main molecule in the ethyl acetate extract. Both extracts exhibited good scavenging activities against DPPH radical (EC50 µg/mL of 59 ± 2 and 31 ± 2 for aqueous and ethyl acetate extracts, respectively). However, the ethyl acetate extract demonstrated more potent quenching activities than the aqueous extract. The antimicrobial activities were assessed on selected Gram-positive (Staphylococcus epidermidis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria, as well as on pathogenic fungus Candida glabrata. The extracts possessed selective and potent antimicrobial activities against the Gram-positive bacterium (IC50 of 186 ± 9 µg/mL and 92 ± 3 µg/mL for aqueous and ethyl acetate extracts, respectively). Finally, C. villosus extracts were evaluated for their antiproliferative potential on three human cancer cell lines representing breast and colon cancers. Although both extracts demonstrated sufficient growth inhibition of the three different cell lines, the ethyl acetate extract exhibited higher activity (LD50 values of 1.57 ± 0.06 mg/mL, 2.2 ± 0.1 mg/mL, and 3.2 ± 0.2 mg/mL for T47D, MCF-7, and HCT-116 cell lines). Both the extracts obtained from the aerial parts of C. villosus revealed very promising results and could be applied as functional agents in the food, pharmaceutical, and cosmeceutical industries.

Design, Synthesis and Anticancer Screening of Novel Benzothiazole-Piperazine-1,2,3-Triazole Hybrids.

A library of novel regioselective 1,4-di and 1,4,5-trisubstituted-1,2,3-triazole based benzothiazole-piperazine conjugates were designed and synthesized using the click synthesis approach in the presence and absence of the Cu(I) catalyst. Some of these 1,2,3-triazole hybrids possess in their structures different heterocyclic scaffold including 1,2,4-triazole, benzothiazole, isatin and/or benzimidazole. The newly designed 1,2,3-triazole hybrids were assessed for their antiproliferative inhibition potency against four selected human cancer cell lines (MCF7, T47D, HCT116 and Caco2). The majority of the synthesized compounds demonstrated moderate to potent activity against all the cancer cell lines examined. Further, we have established a structure activity relationship with respect to the in silico analysis of ADME (adsorption, distribution, metabolism and excretion) analysis and found good agreement with in vitro activity.