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Background. The aim of this study was the clinical and laboratory evaluation of using polycaprolactone (PCL) nanofibers loaded with oxytetracycline hydrochloride (OTC) and zinc oxide (ZnO) as an adjunct to mechanical therapy in managing stage II grade A periodontitis patients concerning GCF lipocalin2- levels. Methods. Fifty stage II grade A periodontitis patients (27 women and 23 men, with an age range of 30‒60) were enrolled in the study. The patients were randomly assigned to five equal groups and treated with scaling and root planing (SRP), followed by local application of PCL nanofibers: group I: SRP + PCL loaded with OTC and ZnO, group II: SRP + PCL loaded with OTC, group III: SRP + PCL loaded with ZnO, group IV: SRP + unloaded PCL, and group V: SRP alone. Additionally, 10 healthy subjects with healthy periodontium (group VI) (age- and gender-matched) served as the negative control. Nanofibers were applied in the selected pockets of periodontitis patients in groups I to IV once weekly for two months. All the participants were examined clinically by assessing periodontal indices (gingival index, plaque index, pocket depth, and clinical attachment level), and biochemically by assessing GCF lipocalin-2 levels. Results. Compared to controls, periodontitis groups (I, II, III, IV, and V) showed significant elevation of both clinical parameters and GCF lipocalin2- levels at baseline. In addition, these parameters improved significantly after treatment, which was more pronounced in groups I, II-, and III) compared to groups IV and V. However, it did not reach normal values. Conclusion. In association with SRP, PCL nanofibers loaded with OTC and ZnO had beneficial therapeutic effects at both clinical and laboratory levels.

Metformin is one of the most prescribed agents in the treatment of type 2 diabetes. Its history goes back to the use of goat’s rue (Galega officinalis Linn., Fabaceae). G. officinalis is rich in galegine, a guanidine derivative with a blood glucose-lowering effect. Research based on the effects of guanidine rich on this traditional herbal medicine led to the development of metformin. Metformin continues to serve as a multi-target drug. Its benefits for treating/controlling several diseases were thoroughly discovered over time. These include health disorders such as cancers, obesity, periodontitis, cardiovascular, liver, skin, and renal disorders. Moreover, there is evidence to propose that metformin postpones the aging processes as well as modulates the microbiota to promote better health. So far, it is not fully understood, how metformin can accomplish such pleiotropic pharmacological and therapeutic effects. Metformin may decrease malignancy via suppressing the signal of insulin/IGF-1, avoiding the release of cytokines via NF-κB, and increasing the immune reaction to cancer cells. This chapter discusses the history of metformin discovery, chemistry, its role in diabetic patients, and proposed molecular mechanisms to shed more light on the diverse effects and its ability to target multiple signaling pathways.

Plant-derived natural products represent a significant source of green chemical compounds. The fruit extract of Emblica officinalis Gaertn., a traditionally used medicinal plant, was exploited in green synthesis of silver nanoparticles (AgNPs) using AgNO3 reduction method. Characterization of the synthesized AgNPs was achieved using UV–Vis, FTIR spectroscopy as well as transmission electron microscopy (TEM). The antioxidant and cytotoxic activities of the extract and AgNPs were investigated. The synthesized AgNPs exhibited moderate inhibition of ABTS•+ (67.2%) compared to the fruit extract (89.9%) and L-ascorbic acid (90.7%). Likewise, the extract exhibited higher cytotoxicity against MCF-7 and HCT-116 (IC50 25 and 20 µg/mL, respectively) compared to AgNPs (IC50 75 and 80 µg/mL, respectively). These results indicated that the functional groups of the biomolecules were quenched during the Ag+ reduction and surface capping processes. Phytochemical investigation of the active extract led to the isolation of a new hexagalloyl derivative designated as emblifatmin (E4), in addition to four known compounds, namely trans-cinnamic acid (E1), methyl gallate (E2), gallic acid (E3), and quercetin-3-O-α-arabinofuranoside (E5), identified by MS and NMR spectroscopy. The new compound, emblifatmin showed a remarkable AgNPs synthetic capability (minimum active concentration, MAC 0.0019 mg/mL) and considerable ABTS•+ antioxidant activity (83.9%).

Seven alkaloids of indole nucleus were isolated from Rhazya stricta (Apocynaceae). Two of which are new epi-rhazyaminine (1) and 20-epi-sitsirikine (2), while the rest are known; eburenine (3), strictamine (4), (16 R)-E-isositsirikine (5), antirhine (6), and strictanol (7). The chemical structures of the isolated compounds were elucidated by interpretation of the obtained spectral data 1D (1H, 13C and DEPT) and 2D (COSY, HSQC, HMBC and NOESY) NMR, UV, IR and MS. Compounds 1-7 were tested against three cancer cell lines; human colorectal carcinoma (HCT-116), prostate cancer (PC-3), human hepatocellular liver carcinoma (HepG2) and normal adult African green monkey kidney (VERO).

The present work provided in vitro anticancer investigation of novel spirooxindole based benzimidazole scaffold SP1 and its nanoformulation with in vivo evaluation of anticancer and antimetastatic activity as potential drug for breast adenocarcinoma. The synthesized compound SP1 exhibited potent growth inhibitory efficacy against four types of human cancer (breast, prostate, colon and lung) cell lines with IC50 = 2.4, 3.4, 7.24 and 7.81 µM and selectivity index 5.79, 4.08, 1.93 and 1.78 respectively. Flow cytometric analysis illustrated that SP1 exhibited high apoptotic effect on all tested cancer cell lines (38.22–52.3 %). The mode of action of this promising compound was declared by its ability to upregulate the gene expression of p21 (2.29–3.91 folds) with suppressing cyclin D (1.9–8.93 folds) and NF-κB (1.26–1.44 fold) in the treated cancer cells. Also, it enhanced the protein expression of apoptotic marker p53 and moderate binding affinity for MDM2 (KD;7.94 μM). Notwithstanding these promising impressive findings, its selectivity against cancer cell lines and safety on normal cells were improved by nanoformulation. Therefore, SP1 was formulated as ultra-flexible niosomal nanovesicles (transethoniosomes). The ultra-deformability is attributable to the synergism between ethanol and edge activators in improving the flexibility of the nanovesicular membrane. F8 exhibited high deformability index (DI) of (23.48 ± 1.4). It was found that % SP1 released from the optimized transethoniosomal formula (F8) after 12 h (Q12h) was 84.17 ± 1.29 % and its entrapment efficiency (%EE) was 76.48 ± 1.44 %. Based upon the very encouraging and promising in vitro results, an in vivo study was carried out in female Balb/c mice weighing (15–25 g). SP1 did halt the proliferation of breast cancer cells as well as suppressed the metastasis in other organs like liver, lung and heart.

Ovarian cancer (OC) is the 7th most common cancer in women world-wide and the 3rd most common female cancer. For the treatment of OC, there is no successful therapeutic. The medications that are currently available have significant side effects and a low therapeutic index. This work aimed to evaluate the anticancer activity of organoselenium pseudopeptide compound against OC cell lines. After treatment with 50 ​μM of compound

Purpose The current study aimed to discuss the potential of nanospanlastics as a surfactant-based vesicular system for improving the topical delivery of 3-acetyl-11-keto-β-boswellic acid (AKBA). AKBA is a potent anti-inflammatory drug, but it has poor oral bioavailability due to its poor aqueous solubility. Moreover, the topical delivery of AKBA is difficult due to its high lipophilicity. To overcome these drawbacks, AKBA was formulated as deformable elastic nanovesicles and nanospanlastics, for improving its topical delivery. Materials and methods AKBA-loaded spanlastic nanovesicles (SNVs) were formulated by ethanol injection technique according to 23 factorial design using Span 60 as a non-ionic surfactant and Tween 80 as edge activator (EA) to investigate the effect of different independent variables on entrapment efficiency (EE%), % drug released after 8 hr (Q8h) and particle size (PS) using Design-Expert software. In vitro characterization, stability test and ex vivo permeation study of the optimized formula were performed. Results The choice of the optimized formula was based on the desirability criteria.‎ F7 was selected as the optimized formula because it has the highest desirability value of 0.648. F7 exhibited EE% of 90.04±0.58%, Q8h of 96.87±2.67%, PS of 255.8±2.67 nm, and zeta potential of -49.56 mV. F7 appeared as spherical well-defined vesicles in both scanning electron microscope (SEM) and transmission electron microscope (TEM). The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies investigated the absence of interaction between AKBA and ‎different excipients and good encapsulation of AKBA within SNVs. F7 retained both physical and chemical stability after storage for 3 months at 4-8 °C. Ex vivo permeation test exhibited significant enhancement of permeability of F7 across rat skin than the free drug. Conclusion Nanospanlastics could be a promising approach for improving the permeability and topical delivery of AKBA.

The ability of quinoline alkaloids (cinchonine, cinchonidine, quinine, and quinidine) to sensitize different human cancer cell lines to doxorubicin (DOX)-induced cell death was evaluated. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the alkaloids ability to enhance DOX-induced apoptosis was explored using Western blotting analysis. Also, flow cytometry was applied to analyze cell fractions in the different cell cycle phases. All alkaloids showed a significant enhancement of DOX-induced cell death in HeLa and HepG2 cell lines. The chemosensitizing activity of the quinoline alkaloids was attributed to the induction of apoptosis as indicated by splitting of caspase-3 and its substrate poly (ADP-ribose) polymerase (PARP). In addition, there was an increase in the cell fractions in sub-G0/G1 phase in case of DOX combination with the alkaloids. This study proves the ability of the quinoline alkaloids to enhance DOX-induced apoptotic cell death in human cervical and hepatocellular carcinoma cells.

Vanillin (1), the main constituent of vanilla species, was used as a starting natural scaffold for the synthesis of five new (2–6) and one known (7) triazole derivatives via click chemistry using the copper (I)-catalyzed azide–alkyne cycloaddition method. Vanillin and its new derivatives; 4-{1-[2-Hydroxymethyl-5-(5 methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl]-1H[1,2,3]triazol-4-ylmethoxy}-3-methoxy-benzaldehyde (2); [4-(4-Formyl-2methoxy-phenoxymethyl)-[1,2,3]triazol-1-yl]-acetic acid methyl ester (3); 4-[1-(4-Acetyl-phenyl)-1H-[1,2,3]triazol-4-ylmethoxy]-3-methoxy-benzaldehyde (4); 4-[4-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethoxy)-3-methoxy-phenyl]-but-3-en-2-one (5); and 4-[4-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethoxy)-3-methoxy-phenyl]-4-hydroxy-butan-2-one (6), as well as the previously known derivative (7) were subjected to antimicrobial, antiquorum-sensing and cytotoxic evaluation. Compounds 4–7 possessed the most notable enhancement in the anti-bacterial activity against Bacillus cereus, Pseudomonas aeruginosa and antifungal activity against Candida albicans. However, compounds 1 and 2 exhibited high antiquorum-sensing activity against Chromobacterium violaceum using catechin as a positive control. Compounds 4–7 demonstrated selective cytotoxicity against MCF-7 and HepG2 cancer cells compared to normal lung fibroblast cells (WI-38). These findings proved the usefulness of synthesis bioactive derivatives from vanillin through chemical modifications.

Purpose: To biosynthesize silver nanoparticles (AgNPs) using Psidium guajava L. and Lawsonia inermis L. leaf extracts, and investigate their antioxidant and cytotoxic activities.Methods: The aqueous extracts were prepared by maceration in distilled H2O followed by partitioning with EtOAc. AgNPs were prepared by treating the extracts with 1 mM AgNO3 and then were characterized by UV-vis and FTIR analyses, and transmission electron microscopy (TEM). MTT cytotoxicity and 2,2`-azinobis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) antioxidant assays were used to assess their cytotoxic and antioxidant properties, respectively.Results: AgNPs from P. guajava and L. inermis extracts exhibited good morphological stability and showed moderate antioxidant activity (68.1 and 71.9%, respectively) compared to their extracts. Equipotent cytotoxicity against HCT-116 and MCF-7 cells was observed for AgNPs derived from P.guajava, while AgNPs derived from L. inermis possessed two-fold cytotoxicity compared to their corresponding extracts. Phytochemical analysis of P. guajava afforded pyrogallol, quercetin, quercetin-3-O-β-xylopyranoside, quercetin-3-O-β-arabinopyranoside, and quercetin-3-O-α-rabinofuranoside, while L. inermis afforded lawsone and luteolin.Conclusion: Flavonoids and phenolics play a major role in reducing Ag+ ions, surface coating, antioxidant, and cytotoxic activities of AgNPs. The biocompatible AgNPs produced by L. inermis demonstrate promising cytotoxic activity that could contribute to new cancer treatments.

Radiopharmaceutical material is a pharmaceutical product or drug that may exert spontaneous degradation of unstable nuclei with nuclear particles or photons emission. Radiopharmaceuticals may be used in research, diagnosis, therapy, and environmental purposes. Moreover, radiopharmaceuticals act as radioactive tracers among patients via gamma-ray emissions. Therefore, the uses of radiopharmaceuticals as diagnostic agents may be given to patients to examine any biochemical, molecular biology, physiological, or anatomical abnormalities. Therapeutic radiopharmaceutical may be administered internally for therapeutic purposes via selective effect on certain abnormal cells or organs. The best known example for therapeutic radiopharmaceuticala is iodide131 for thyroid ablation in among patients with hyperthyroid. A third class of radiopharmaceutical is drug labeling which mainly used in research by using small amount of radioactive substances not for diagnostic purposes, but to investigate the metabolism, bio-distribution, pharmakodynamic, and pharmakokinetic of certain drugs in a nonradioactive form. This chapter focuses mainly on basic fundamentals of radiopharmaceutical chemistry, preparation, environmental, pharmaceutical, diagnostic, therapeutic, and research applications.

Rhazya stricta is a rich indole alkaloid medicinal plant species, that is used in traditional medicine particularly in Middle East countries to treat inflammations, diabetes, rheumatism, and skin disorders. The alkaloid plant extract of R. stricta was fractionated on aluminum oxide column and further purified by different chromatographic methods. The chemical structures of the isolated compounds were elucidated by interpretation of their 1D and 2D NMR, IR, UV and MS spectral data. The potential antitumor effect was examined against three cancer cell lines; HCT-116-colon cancer, PC-3-prostate cancer and HepG2-liver cancer as well as a control cell line (Vero) using MTT assay. Two new indole alkaloids, identified as 16-epi-stemmadenine-N-oxide (1) and stemmadenine-N-methyl (2), along with the known indole alkaloid 20-epi-antirhine (3) were isolated from the leaves of Rhazya stricta. Compound 2, stemmadenine-N-methyl exhibited a reasonable selectivity index and a broad anticancer effect against the examined cell lines with IC50 35.0±0.7, 35.0±0.6, 40.0±0.7and 79.0±1.0 μM, respectively. Furthermore, the effect of stemmadenine-N-methyl was evaluated on cell migration using woundhealing assay. It significantly hindered cell migration and delayed-wound healing. 16-epistemmadenine- N-oxide and stemmadenine-N-methyl are new indole alkaloids isolated from the leaves of Rhazya stricta, of which stemmadenine-N-methyl selectively inhibited the proliferation of three different cancer cell lines. In addition, it prevented cell migration and delayed wound-healing. Further studies are required to confirm the mechanism by which this promising alkaloid exhibits its antitumor activity.

The Michael addition reaction of barbituric acid with chalcones incorporating the indole scaffold was achieved by using a highly efficient bimetallic Iron–palladium catalyst in the presence of acetylacetone (acac). This catalytic approach produced the desired products in a simple operation and low catalyst loading with acceptable yield of the new hybrids. All tested compounds were subjected for biological activity on α‐glucosidase and α‐amylase. The results revealed that all synthesized compounds exhibited very good activity against both enzymes when compared to positive control (acarbose). Moreover, compound 5o showed the best activity whereas its IC50 (μM) are 13.02+0.01 and 21.71+0.82 for α‐glucosidase and α‐amylase respectively. Both compounds 5o and 5l exhibited high similarity in binding mode and pose with amylase protein (4UAC). The obtained data may be used for developing potential hypoglycemic agents.

The hepatoprotective activities of two traditionally used plants, Cleome droserifolia (Forssk.) Delile, Cleomaceae, and Artemisia annua L., Asteraceae, were recently reported. However, the biologically active metabolites responsible for this activity were not identified. The aqueous extract of C. droserifolia aerial parts, and the polar fraction of A. annua leaves were screened for their antioxidant activities using the 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) assay. The in vitro viability of HepG-2 cells treated with CCl4 and the extracts were assessed by MTT assay. The effects of the extracts on the liver enzymes and the total soluble protein in CCl4-intoxicated HepG-2 cells were investigated. An HPLC/PDA/ESI/MS–MS based analysis was carried out for extract of C. droserifolia and polar fraction of A. annua. Both exhibited pronounced free radical scavenging activities (86 and 83%, respectively). Both showed a significant increase in cell viability: 86.43% for the extract of C. droserifolia and 79.32% for polar fraction of A. annua. Only the extract of C. droserifolia (39.6 ± 5.41 and 20.4 ± 6.91 IU/dl, respectively) and polar fraction of A. annua (40.8 ± 2.14 and 24.5 ± 3.11 IU/dl, respectively) restored the levels of liver enzymes (aspartate transaminase and alanine transaminase, respectively) compared to the CCl4 intoxicated group (87.5 ± 4.34 and 34.1 ± 8.12 IU/dl, respectively) and other herbal extracts. More than fifty phenolic secondary metabolites were identified in the extracts under investigation. The significant hepatoprotective activities of both extracts seemed to be strongly connected to their content of hydroxycinnamoyl quinic acids and flavonoids. Keywords: Herb, Traditional, HPLC/PDA/ESI/MS–MS, Hepatoprotective, HepG-2, Antioxidant

Anticancer therapeutics with profiles of high potency, low toxicity, and low resistance is of considerable interest. A new series of functionalized spirooxindole linked with 3-acylindole scaffold is reported, starting from chalcones derived from 3-acetyl indole with isatin, and l-4-thiazolidinecarboxylic acid. The reactions proceeded regioselectivity, stereoselectivity, without side products in high yield (71–89%). The new spirooxindole hybrids have been evaluated in vitro for their antiproliferative effects against colon cancer (HCT-116), hepatocellular carcinoma (HepG2) and prostate cancer (PC-3). The selectivity of their activity was evaluated. Some of the synthesized compounds showed considerable anticancer activities. Compound 4k proved to retain a high cytotoxic activity and selectivity against colon cancer cells HCT-116 (IC50 = 7 ± 0.27 µM, SI: 3.7), and HepG2 (IC50 = 5.5 ± 0.2 µM, SI: 4.7) in comparison to (IC50 = 12.6 ± 0.5, SI: 0.4 and 5.5 ± 0.3 µM, SI: 0.9, respectively). Compound 4k was less active (IC50 = 6 ± 0.3 µM, SI: 4.3) than cisplatin (IC50 = 5 ± 0.56 µM, SI: 1.0) but showed greater selectivity towards prostate cancer cells PC-3 in comparison to cisplatin. The details of the binding mode of the active compounds were clarified by molecular docking. Ligand Efficiency (LE) and Ligand Lipophilic Efficiency (LLE) were evaluated and revealed that compound 4k had acceptable value.

The natural product piperine, the major bioactive alkaloid present in black pepper fruits, has the ability to modulate the functional activity of several biological targets. In this study, we have utilized the natural piperine as a tail moiety to develop new SLC-0111 analogues (6a-d, 8 and 9) as potential carbonic anhydrase inhibitors. Thereafter, different functionalities, free carboxylic acid (11a-c), acetyl (13a) and ethyl ester (13b-c), were exploited as bioisosteres of the sulfamoyl functionality. All piperine-based derivatives were assessed for their inhibitory actions against four human (h) CA isoforms: hCA I, II, IX and XII. The best hCA inhibitory activity was observed for the synthesized primary piperine-sulfonamides (6a-d and 8). In particular, both para-regioisomers (6c and 8) emerged as the most potent hCA inhibitors in this study with two-digit nanomolar activity against hCA II (KIs = 93.4 and 88.6 nM, respectively), hCA IX (KIs = 38.7 and 68.2 nM, respectively), and hCA XII (KIs = 57.5 and 45.6 nM, respectively). Moreover, piperine-sulfonamide 6c was examined for its anti-cancer and pro-apoptotic actions towards breast MCF-7 cancer cell line. Collectively, piperine-based sulfonamides could be considered as a promising scaffold for development of efficient anticancer candidates with potent CA inhibitory activities.