SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY OF POLYMER NICKEL (II) COMPLEX

4-vinyl pyridine nickel complex containing polymerizable vinyl group, prepared by condensing (4:1 molar ratio) of 4-vinylpyridine with Nickel chloride, then polymerized with methyl methacrylate at 70 °C using AIBN as initiator. Metal complexand polymer metal complex have been characterized by elemental analyses, molar conductance, IR, 1H-NMR , Massspectra and thermal analyses (DTA and TGA). Conductivity measurement reveals the nonelectrolytic nature of thecomplex. This confirms that, the anion is coordinated to the metal ion. The IR reveal the metal ion is coordinated via thenitrogen atom of 4-VP. Nickel complex and polymer nickel complex have been tested invitro against number of tumor andnumber of microorganisms in order to assess their anti tumor and antimicrobial properties. The antimicrobial activity wasobserved by compounds VP-Ni and MMA-VP-Ni under the screening conditions. The activity against HCT-116 cells wasdetected for compound VP-Ni (with IC50 value 9.8±0.6 µg/ml), compared with reference standard (24.6±0.3 µg/ml) followedby MMA-VP-Ni (48.3±1.5). In conclusion, this study highlighted the synthesis of polymer nickel complex, and proved thepromising biological activity of the synthesized compounds

Evaluation of Antimicrobial bioactive compounds from Endophytic Fungi Isolated from Moringa oleifera

Endophytic fungi are microorganisms that inhabit the living tissues of their host plants without causing any host loss. They are considered as a continuous natural source of novel bioactive secondary metabolites with potential application in medicine, which are almost same to their host plant. In this study a total of nine endophytic fungal isolates were collected from leaves and stems of Moringa oleifera. Based on the colonization frequency (CF) results, the highest number of isolates was obtained from plant stem, while the least was from leaves. The nine isolates were identified by keeping track of morphological and microscopic observations. Identification of the two antimicrobial potent strains was confirmed by 18S rDNA-based molecular analysis. The nine isolates were found belonging to Chaetomium, Alternaria, Fusarium, Aspergillus, Mycelia, Penicillium and Nigrospora taxa. Among them, Chaetomium taxon was included the highest CF) 40% (. Evaluation of antimicrobial activity documented ethyl acetate fungal extract as the highest effective inhibitor against Gram-negative and Gram-positive bacteria, and Aspergillus fumigatus. Minimum inhibitory concentration (MIC) was examined for the two most potent antimicrobial effective extracts, from Chaetomium laterale and Chaetomium interruptum; it was ranged from 12.5 to 0.39 mg/ml

Novel thiazolidinone/thiazolo[3,2-a] benzimidazolone-isatin conjugates as apoptotic anti-proliferative agents towards breast cancer: One-pot synthesis and in vitro biological evaluation

In connection with our research program on the development of new isatin-based anticancer candidates, herein we report the synthesis of two novel series of thiazolidinone-isatin conjugates (4a-n) and thiazolo[3,2-a]benzimidazolone-isatin conjugates (7a-d), and in vitro evaluation of their antiproliferative activity towards two breast cancer cell lines; triple negative MDA-MB-231, and MCF-7. Compounds 4m and 7b emerged as the most active congeners against MDA-MB-231 cells (IC50= 7.6 ± 0.5 and 13.2 ± 1.1 µM, respectively). Compounds 4m and 7b were able to provoke apoptosis in MDA-MB-231 cells, evidenced by the up-regulation of Bax and down-regulation of Bcl-2, besides boosting caspase-3 levels. Hybrid 4m induced a fourfold increase in the percentage of cells at Sub-G1, with concurrent arrest in G2-M phase by 2.5-folds. Furthermore, hybrid 4m resulted in a sixfold increase in the percentage of annexin V-FITC positive apoptotic MDA-MB-231 cells as compared with the control. Moreover, the cytotoxic activities of the active conjugates were assessed towards two nontumorigenic cell lines (breast MCF-10A and lung WI-38) where both conjugates 4m and 7b displayed mean tumor selectivity index: 9.6 and 13.9, respectively. Finally, several ADME descriptors were predicted for the active conjugates via a theoretical kinetic study

Synthesis of Novel Chalcone-Based Phenothiazine Derivatives as Antioxidant and Anticancer Agents

Based on reported results for the potential medicinal impact of phenothiazine core, as well as the chalcone skeleton that is widely present in many natural products, together with their reported bioactivities, the present work was aimed at combining both moieties in one molecular skeleton and to synthesize and characterize a novel series of chalone-based phenothiazine derivatives. For this purpose, 2-acetylphenothiazine was N-alkylated, followed by the Claisen-Schmidt reaction to produce the chalcones with good yield. Antioxidant activity, as evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, was assessed to determine if their antioxidant potential was comparable with ascorbic acid, and attributable to the phenothiazine core. Screening anticancer activities of the synthesized chalone-based phenothiazine derivatives against human breast cancer cell line MCF-7 cells, and human hepatocellular carcinoma HepG-2 cells, compared with standard drugs cisplatin and doxorubicin, was evaluated. The results revealed that compounds 4a, 4b, 4d, 4h, 4j, 4k, 4m, 4o, and 4p were good against human hepatocellular carcinoma HepG-2 cells, and among these compounds 4b and 4k were the most effective compounds, with IC50 values of 7.14 μg/mL and 7.6 1 μg/mL, respectively. On the other hand, compounds 4a, 4b, 4k, and 4m were good against human breast cancer cell line MCF-7 cells and, among these compounds, 4k and 4b were the most effective compounds, with IC50 values of 12 μg/mL and 13. 8 μg/mL, respectively. The overall results suggest that these compounds could, potentially, be further modified for the formation of more potent antioxidant and anticancer agents

Antimicrobial and anticancer evaluation of a novel synthetic tetracyclic system obtained by Dimroth rearrangement

A series of pyrido[3',2':4,5]thieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidines were prepared via oxidative cyclization of 4-(2-arylidenehydrazinyl)pyrido [3',2':4,5]thieno[3,2-d] pyrimidines. Dimroth rearrangement of such a series yielded pyrido[3',2':4,5]thieno[2,3-e][1,2,4]triazolo[1,5-c]pyrimidines. The reaction mechanism was proposed and the products were screened for their antimicrobial and anticancer activities. From the antimicrobial screening results, it can be seen that compounds 8c, 9f and 10c showed excellent activity against gram positive bacteria while compounds 10d and 8c showed the highest activity against gram negative bacteria. The results of the anticancer activities showed that compound 9c was the most active against HepG-2 and MCF-7 with IC50 values of 1.19 and 3.46, respectively

Antimicrobial and anticancer activity of some novel fluorinated thiourea derivatives carrying sulfonamide moieties: synthesis, biological evaluation and molecular docking

Abstract Background Various thiourea derivatives have been used as starting materials for compounds with better biological activities. Molecular modeling tools are used to explore their mechanism of action. Results A new series of thioureas were synthesized. Fluorinated pyridine derivative 4a showed the highest antimicrobial activity (with MIC values ranged from 1.95 to 15.63 µg/mL). Interestingly, thiadiazole derivative 4c and coumarin derivative 4d exhibited selective antibacterial activities against Gram positive bacteria. Fluorinated pyridine derivative 4a was the most active against HepG2 with IC50 value of 4.8 μg/mL. Molecular docking was performed on the active site of MK-2 with good results. Conclusion Novel compounds were obtained with good anticancer and antibacterial activity especially fluorinated pyridine derivative 4a and molecular docking study suggest good activity as mitogen activated protein kinase-2 inhibitor. Graphical abstract Compound 4a in the active site of MK-

Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety

Abstract Background A series of novel N-(2, 6-dimethoxypyrimidin-4-yl)-4-(3-(aryl)thioureido) benzenesulfonamides 3a–t was synthesized by the addition of N-(2,6-dimethoxypyrimidin-4-yl)-4-isothiocyanatobenzenesulfonamide 2 to the appropriate aromatic amine. The structures of the synthesized compounds were inspired from the second line antituberculosis pro-drugs. Results Most of the new compounds were screened for their activity against Mycobacterium tuberculosis. The results of the antimycobacterial assay showed that compound 3i exerted the highest activity (MIC = 3.13 µg/mL), followed by compound 3s (MIC = 6.25 µg/mL). Conclusion The structure–activity relationship (SAR) analysis revealed that the introduction of the benzo[1,3]dioxol moiety in 3i and the 4-morpholinyl-4-phenyl moiety in 3s has proven to give the most potent compounds in this study. Docking of the promising compounds inside the active site of M. tuberculosis enoyl reductase InhA was performed in order to emphasize the results. The compounds showed a similar orientation to that of GSK 625 inside the active site of 5JFO and bind to Met 98 in a way similar to that of the co-crystallized ligand

Novel Thiazolidinone/Thiazolo[3,2-a]Benzimidazolone-Isatin Conjugates as Apoptotic Anti-proliferative Agents Towards Breast Cancer: One-Pot Synthesis and In Vitro Biological Evaluation

In connection with our research program on the development of new isatin-based anticancer candidates, herein we report the synthesis of two novel series of thiazolidinone-isatin conjugates (4a–n) and thiazolo[3,2-a]benzimidazolone-isatin conjugates (7a–d), and in vitro evaluation of their antiproliferative activity towards two breast cancer cell lines; triple negative MDA-MB-231, and MCF-7. Compounds 4m and 7b emerged as the most active congeners against MDA-MB-231 cells (IC50 = 7.6 ± 0.5 and 13.2 ± 1.1 µM, respectively). Compounds 4m and 7b were able to provoke apoptosis in MDA-MB-231 cells, evidenced by the up-regulation of Bax and down-regulation of Bcl-2, besides boosting caspase-3 levels. Hybrid 4m induced a fourfold increase in the percentage of cells at Sub-G1, with concurrent arrest in G2-M phase by 2.5-folds. Furthermore, hybrid 4m resulted in a sixfold increase in the percentage of annexin V-FITC positive apoptotic MDA-MB-231 cells as compared with the control. Moreover, the cytotoxic activities of the active conjugates were assessed towards two nontumorigenic cell lines (breast MCF-10A and lung WI-38) where both conjugates 4m and 7b displayed mean tumor selectivity index: 9.6 and 13.9, respectively. Finally, several ADME descriptors were predicted for the active conjugates via a theoretical kinetic study