Synthesis and evaluation of novel almazole D analogs as anticancer agents.

Novel almazole D-amide conjugates, esters, and N-alkylated analogs were synthesized and investigated for their anticancer activity against seven cancer cell lines. Among the series, compounds 5g and 5m showed significant anticancer activities against multiple cell lines with moderate selectivity indices. Compound 5g had IC50 values of 5.86 ± 0.31, 9.94 ± 0.06, 12.74 ± 0.12, and 9.40 ± 0.03 µM against the B16-F10, DU145, HeLa, and LC-540 cell lines, respectively, while compound 5m showed IC50 values of 6.35 ± 0.09, 9.17 ± 0.11, 9.00 ± 0.011, 19.65 ± 0.63, 8.13 ± 0.04, and 11.56 ± 0.01 µM against B16-F10, DU145, HeLa, HepG2, LC-540, and SK-BR-3 cells, respectively. Compared to almazole D, which only showed significant activity against B16-F10 cells (IC50 = 9.05 ± 0.008 µM), the synthesized analogs showed improved anticancer activity against multiple cell lines. The kinase inhibition assay coupled with the docking studies revealed that epidermal growth factor receptor (EGFR) kinase inhibition via interaction with amino acid residue T790 on the EGFR is one of the possible mechanisms by which 5g exerts its anticancer potential. The ADMET prediction and drug-likeness of the analogs project the synthesized analogs as promising agents, which can be further developed for application in cancer therapy.

Synthesis and characterization of novel combretastatin analogues of 1,1-diaryl vinyl sulfones, with antiproliferative potential via in-silico and in-vitro studies.

Novel 1,1-diaryl vinyl-sulfones analogues of combretastatin CA-4 were synthesized via Suzuki-Miyaura coupling method and screened for in-vitro antiproliferative activity against four human cancer cell lines: MDA-MB 231(breast cancer), HeLa (cervical cancer), A549 (lung cancer), and IMR-32 (neuroblast cancer), along with a normal cell line HEK-293 (human embryonic kidney cell) by employing 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The compounds synthesised had better cytotoxicity against the A549 and IMR-32 cell lines compared to HeLa and MDA-MB-231 cell lines. The synthesized compounds also showed significant activity on MDA-MB-231 cancer cell line with IC50 of 9.85-23.94 µM, and on HeLa cancer cell line with IC50 of 8.39-11.70 µM relative to doxorubicin having IC50 values 0.89 and 1.68 µM respectively for MDA-MB-231 and HeLa cell lines. All the synthesized compounds were not toxic to the growth of normal cells, HEK-293. They appear to have a higher binding affinity for the target protein, tubulin, PDB ID = 5LYJ (beta chain), relative to the reference compounds, CA4 (- 7.1 kcal/mol) and doxorubicin (- 7.2 kcal/mol) except for 4E, 4M, 4N and 4O. The high binding affinity for beta-tubulin did not translate into enhanced cytotoxicity but the compounds (4G, 4I, 4J, 4M, 4N, and 4R, all having halogen substituents) that have a higher cell permeability (as predicted in-silico) demonstrated an optimum cytotoxicity against the tested cell lines in an almost uniform manner for all tested cell lines. The in-silico study provided insight into the role that cell permeability plays in enhancing the cytotoxicity of this class of compounds and as potential antiproliferative agents.

Effect of operational parameters, characterization and antibacterial studies of green synthesis of silver nanoparticles using Tithonia diversifolia.

BACKGROUND: There is a growing interest in the green synthesis of silver nanoparticles (AgNPs) using plant extract because the technique is cost effective, eco-friendly and environmentally benign. This is phasing out the use of toxic and hazardous chemical earlier reported. Tithonia diversifolia is a wild sunflower that grows widely in the western part of Nigeria with a proven medicinal benefit. However, several studies carried out have left doubts on the basic operational parameters needed for the green synthesis of AgNPs. The objective of this work was to carry out green synthesis of AgNPs using T. diversifolia extract via an eco-friendly route through optimization of various operational parameters, characterization, and antimicrobial studies. METHOD: Green synthesis of TD-AgNPs was done via bottom-up approach through wet chemistry technique using environmentally benign T. diversifolia plant extract as both reducing and stabilizing agent. Phytochemical Screening of the TD plant extract was carried out. Experimental optimization of various operational parameters-reaction time, concentration, volume ratio, and temperature was investigated. TD-AgNPs were characterized by UV-Vis spectroscopy, FTIR Spectroscopy, SEM/energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and transmission electron microscopy (TEM). Antimicrobial studies against multi drug resistant microorganisms (MDRM) were studied using the agar well diffusion method. RESULTS: This study reveals the importance of various operational parameters in the synthesis of TD-AgNPs. Excellent surface plasmon resonance peaks (SPR) were obtained at optimum experimental factors of 90 min reaction time under room temperature at 0.001M concentration with the volume ratio of 1:9 (TD extract:Ag ion solution). The synthesis was monitored using UV-Vis and maximum wavelength obtained at 430 nm was due to SPR. The morphology and elemental constituents obtained by TEM, SEM, and EDX results revealed a spherical shape of AgNPs with prominent peak of Ag at 3.0 kV in EDX spectrum. The crystallinity nature was confirmed by XRD studies. FTIR analysis proved presence of biomolecules functioning as reducing, stabilizing, and capping agents. These biomolecules were confirmed to be flavonoid, triterpenes, and saponin from phytochemical screening. The antimicrobial studies of TD-AgNPs were tested against MDRM-Escherichia coli, Salmonella typhi, Salmonella enterica, and Bacillus subtilis. DISCUSSION: The variation of reaction time, temperature, concentration, and volume ratio played substantive and fundamental roles in the synthesis of TD-AgNPs. A good dispersion of small spherical size between 10 and 26 nm was confirmed by TEM and SEM. A dual action mechanism of anti-microbial effects was provided by TD-AgNPs which are bactericidal and membrane-disruption. Based on the antimicrobial activity, the synthesized TD-AgNPs could find good application in medicine, pharmaceutical, biotechnology, and food science.

Natural antifungal compounds from the peels of Ipomoea batatas Lam.

Three antifungal compounds have been isolated for the first time from the peels of Ipomoea batatas Lam. Their structures were established on the basis of 1D and 2D NMR spectra data as well as ESI-MS and IR analysis. Urs-13(18)-ene-3ß-yl acetate was found to possess a weak activity against Sporothrix schenckii and Trichophyton metagrophytes fungi with an MIC value of 50 µg/mL each. Stigmasterol and 3-friedelanol were equally active against T. metagrophytes.