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Bioassay guided fractionation of the roots of Lantana montevidensis (Verbenaceae) has resulted in the isolation and identification of three new triterpenoids; 13-hydroxy-3-oxo-olean-11-en-28-oic acid (1), 12,13-dihydroxyolean-3-oxo-28-oic acid (2) and 12,13,22-trihydroxyolean-3-oxo-28-oic acid (3) in addition to nine known compounds: oleanonic acid (4), oleanolic acid (5), 3,25-dihydroxy-olean-12-en-28-oic acid (6), lantadene A (7), 19-hydroxy-3-oxo-olean-12-en-28-oic acid (8) pomolic acid (9), camaric acid (10) together with -sitosterol (11) and -sitosterol-3-O--D-glucoside (12). The structures of the isolated metabolites were elucidated based on comprehensive 1D and 2D NMR spectroscopic data as well as HR-ESI–MS. The extracts and the isolated metabolites were evaluated for their antiprotozoal and antimicrobial activities. Compound 2 showed antibacterial activity against Staphylococcus aureus and methicillin resistant S. aureus with IC50 values against both organisms of 2.1 µM and compound 10 showed activity against same organisms with IC50 values 8.74 and 8.09 µM, respectively, compared to the positive control ciprofloxacin (IC50 = 0.3 µM against S. aureus and MRSA). Compounds 1, 4, 5, 6, and 10 showed moderate antileishmanial activity with IC50 values ranging between (2.54–14.95 µM) and IC90 values ranging between (11.90–19.47 µM), using pentamidine as a control (IC50 values 2.09  16.8 µM) and IC90 values ranging between (4.72  16.8 µM). These compounds also showed highly potent antitrypanosomal activity with IC50 values ranging between (0.39–7.12 µM) and IC90 values ranging between (1.91–10.51 µM), which are more efficient than the DFMO, the antitrypanosomal drug employed as positive control (IC50 and IC90 values 11.82 and 30.82 µM).

Bioassay guided fractionation of the roots of Lantana montevidensis (Verbenaceae) has resulted in the isolation and identification of three new triterpenoids; 13-hydroxy-3-oxo-olean-11-en-28-oic acid (1), 12,13-dihydroxyolean-3-oxo-28-oic acid (2) and 12,13,22-trihydroxyolean-3-oxo-28-oic acid (3) in addition to nine known compounds: oleanonic acid (4), oleanolic acid (5), 3,25-dihydroxy-olean-12-en-28-oic acid (6), lantadene A (7), 19-hydroxy-3-oxo-olean-12-en-28-oic acid (8) pomolic acid (9), camaric acid (10) together with -sitosterol (11) and -sitosterol-3-O--D-glucoside (12). The structures of the isolated metabolites were elucidated based on comprehensive 1D and 2D NMR spectroscopic data as well as HR-ESI–MS. The extracts and the isolated metabolites were evaluated for their antiprotozoal and antimicrobial activities. Compound 2 showed antibacterial activity against Staphylococcus aureus and methicillin resistant S. aureus with IC50 values against both organisms of 2.1 µM and compound 10 showed activity against same organisms with IC50 values 8.74 and 8.09 µM, respectively, compared to the positive control ciprofloxacin (IC50 = 0.3 µM against S. aureus and MRSA). Compounds 1, 4, 5, 6, and 10 showed moderate antileishmanial activity with IC50 values ranging between (2.54–14.95 µM) and IC90 values ranging between (11.90–19.47 µM), using pentamidine as a control (IC50 values 2.09  16.8 µM) and IC90 values ranging between (4.72  16.8 µM). These compounds also showed highly potent antitrypanosomal activity with IC50 values ranging between (0.39–7.12 µM) and IC90 values ranging between (1.91–10.51 µM), which are more efficient than the DFMO, the antitrypanosomal drug employed as positive control (IC50 and IC90 values 11.82 and 30.82 µM).

Bioassay guided fractionation of the roots of Lantana montevidensis (Verbenaceae) has resulted in the isolation and identification of three new triterpenoids; 13-hydroxy-3-oxo-olean-11-en-28-oic acid (1), 12,13-dihydroxyolean-3-oxo-28-oic acid (2) and 12,13,22-trihydroxyolean-3-oxo-28-oic acid (3) in addition to nine known compounds: oleanonic acid (4), oleanolic acid (5), 3,25-dihydroxy-olean-12-en-28-oic acid (6), lantadene A (7), 19-hydroxy-3-oxo-olean-12-en-28-oic acid (8) pomolic acid (9), camaric acid (10) together with -sitosterol (11) and -sitosterol-3-O--D-glucoside (12). The structures of the isolated metabolites were elucidated based on comprehensive 1D and 2D NMR spectroscopic data as well as HR-ESI–MS. The extracts and the isolated metabolites were evaluated for their antiprotozoal and antimicrobial activities. Compound 2 showed antibacterial activity against Staphylococcus aureus and methicillin resistant S. aureus with IC50 values against both organisms of 2.1 µM and compound 10 showed activity against same organisms with IC50 values 8.74 and 8.09 µM, respectively, compared to the positive control ciprofloxacin (IC50 = 0.3 µM against S. aureus and MRSA). Compounds 1, 4, 5, 6, and 10 showed moderate antileishmanial activity with IC50 values ranging between (2.54–14.95 µM) and IC90 values ranging between (11.90–19.47 µM), using pentamidine as a control (IC50 values 2.09  16.8 µM) and IC90 values ranging between (4.72  16.8 µM). These compounds also showed highly potent antitrypanosomal activity with IC50 values ranging between (0.39–7.12 µM) and IC90 values ranging between (1.91–10.51 µM), which are more efficient than the DFMO, the antitrypanosomal drug employed as positive control (IC50 and IC90 values 11.82 and 30.82 µM).

Two privileged pharmacophores were assembled in one molecular frame involving 5-aminosalicylate and 4-thiazolinones that can be found in different stereochemical features. The compounds were fully characterized and evaluated for antiproliferative activity against four human cancer cell lines and some are equipotent to doxorubicin with lower cytotoxicity to normal cells. The most interesting finding relates to compound 10, which shows an IC50 value of 70 µM against MCF-7 cells, while the IC50 against human fibroblasts is 10 µM. The results of this study indicate that the new compounds are optimal anti-cancer leading compounds and merit further studies to optimize their structure, detect their biotargets and in vivo activity.

Two privileged pharmacophores were assembled in one molecular frame involving 5-aminosalicylate and 4-thiazolinones that can be found in different stereochemical features. The compounds were fully characterized and evaluated for antiproliferative activity against four human cancer cell lines and some are equipotent to doxorubicin with lower cytotoxicity to normal cells. The most interesting finding relates to compound 10, which shows an IC50 value of 70 µM against MCF-7 cells, while the IC50 against human fibroblasts is 10 µM. The results of this study indicate that the new compounds are optimal anti-cancer leading compounds and merit further studies to optimize their structure, detect their biotargets and in vivo activity.

Two privileged pharmacophores were assembled in one molecular frame involving 5-aminosalicylate and 4-thiazolinones that can be found in different stereochemical features. The compounds were fully characterized and evaluated for antiproliferative activity against four human cancer cell lines and some are equipotent to doxorubicin with lower cytotoxicity to normal cells. The most interesting finding relates to compound 10, which shows an IC50 value of 70 µM against MCF-7 cells, while the IC50 against human fibroblasts is 10 µM. The results of this study indicate that the new compounds are optimal anti-cancer leading compounds and merit further studies to optimize their structure, detect their biotargets and in vivo activity.

Building on the initial successful optimization of a novel series of tetraindoles, a second generation of the compounds with changes in the core phenyl ring was synthesized to improve anticancer properties. 17 new compounds with different rigidity, planarity, symmetry and degree of conjugation of their core structures to 5-hydroxyindole units were synthesized. All the compounds were fully characterized and tested against breast cancer cell line (MDA-MB-231). The results revealed that the core structure is required for activity and it should be aromatic, rigid, planar, symmetrical and conjugated for optimal activity. Compound 29, which has strong anticancer activity against various tumor-derived cell lines, including Mahlavu (hepatocellular), SK-HEP-1 (hepatic), HCT116 (colon), MIA PaCa-2 (pancreatic), H441 (lung papillary), A549 (lung), H460 (non-small cell lung) and CL1-5 (lung carcinoma) with IC50 values ranging from 0.19 to 3.50 µM, was generated after series of successive optimizations. It was found to induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in the non-obese diabetic-severe combined immunodeficiency (NOD/SCID) mice bearing xenografted MIA PaCa-2 human pancreatic cancer.

In order to identify structural features of lithocholic acid (LCA) critical for inhibition of the enzyme sialyltransferase (ST) novel analogues with modifications of the skeleton (7–9, 16–18 and 20) were designed and synthesized. Methyl 3-acetoxy-7-oxo-cholanate (1), methyl 3-acetoxy-12-oxo-cholanate (2) and methyl 3,7-diacetoxy-12-oxo-cholanate (3) were subjected to Baeyer-Villiger oxidation to provide homolactones (7–9) or to the Beckmann rearrangement of the corresponding oximes to give homolactams (16–18). Both reactions proceed regio- and stereoselectively. Ring B homolog of lithocholic acid (20) was efficiently synthesized. Among these compounds, 7, 9 and 16 were found to have the significant activity, with IC50 values  3 µM against -2,6-(N)-ST selectively, which are 5-fold lower than that of Lith-O-Asp. Given the reality that LCA and its analogue, Lith-O-Asp, have been revealed to improve inhibitory efficacy of ST and to have a wide range of antimetastatic activities in different human cancer cells, the up-to-date findings have noteworthy pharmacological significance as they open a promising path to the improvement of a prospective molecular targeted application of modified LCA analogues as agents for the treatment of cancer metastasis.

The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing Metoprolol Tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas, the films were used to increase the drug’s bioavailability via the sublingual route. Niosomes were prepared using Span 60 and Cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using HPMC and MC as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, palatability) of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 min), while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared to that of commercial oral tablet. The plasma levels remained detectable for 24 h following sublingual administration, compared to only 12 h after administration of the oral tablet. In addition, the absolute bioavailability of the drug (i.e. relative to intravenous administration) following sublingual administration was found to be significantly higher (91.06  13.28%), as compared to that after oral tablet administration (39.37  11.4%). These results indicate that the fast dissolving niosomal film could be a promising delivery system to enhance the bioavailability and prolong the therapeutic effect of Metoprolol Tartrate.