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.

Corrigendum to "Antidiabetic, antioxidant and antimicrobial activities of extracts of Tephrosia bracteolata leaves" [Heliyon 5 (8) (August 2019) e02275].

[This corrects the article DOI: 10.1016/j.heliyon.2019.e02275.].

Antidiabetic, antioxidant and antimicrobial activities of extracts of Tephrosia bracteolata leaves.

AIMS: Plant extracts have long been used for the ethnomedical treatment of diabetes, microbial infections and as a source of antioxidant. This study was aimed at investigating the antidiabetic, antioxidant, and antimicrobial activities of the n-hexane and ethyl acetate extract of Tephrosia bracteolata leaves (TBL) as associated with the ethnobotanical knowledge of the local people of Nigeria. MAIN METHODS: The phytochemical composition of the n-hexane and ethyl acetate extract of the leaves of T. bracteolata were determined following standard procedures in literature, and it's in vitro inhibitory activities against α-glucosidase enzyme. 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS.+) and 1,1-diphenyl-2-picrylhydrazyl (DPPH+) antioxidant activities were also examined. Well diffusion method was employed in evaluating the antimicrobial property of the extracts. KEY FINDINGS: The ethyl acetate extract of T. bracteolata leaves had the greatest inhibitory effect on α-glucosidase, followed by the n-hexane with IC50 43.95 µg/ml and IC50 ˃50 µg/ml respectively. The ethyl acetate also exhibited significant DPPH+ and ABTS.+ antioxidant activity with IC50 of 24.96 µg/ml and 6.48 µg/ml as compared to Ascorbic acid and Trolox (12.24 µg/ml and 5.91 µg/ml) respectively. The zones of inhibition of the ethyl acetate extract of T. bracteolata leaves ranges from 10 - 25 mm at a concentration of 6.25-200 mg/ml, and it showed a greater antibacterial activity than the n-hexane extract, having a zone of inhibition from 10 - 20 mm at concentration of 12.5-200 mg/ml when compared to the standard Gentamycin. Similarly, the ethyl acetate extract of T. bracteolata showed a better anti fungi activity at concentration range 12.5-200 mg/ml than the n-hexane extract at concentration range of 25-200 mg/ml with reference to Tioconazole. These results indicated for the first time that the ethyl acetate extract of T. bracteolata leaves extracts exerted potent inhibitory effects against α-glucosidase, actively scavenge DPPH+ and ABTS.+ free radicals and successfully inhibits the proliferation of Gram positive and Gram negative microorganism. SIGNIFICANCE: TBL is an important source of antidiabetic, antimicrobial and antioxidant agent.

Isolation and antiproliferative activity of triterpenoids and fatty acids from the leaves and stem of Turraea vogelii Hook. f. ex benth.

Chloroform extract from the leaves of Turraea vogelii Hook f. ex Benth demonstrated cytotoxic activity against a chronic myelogenous leukemia cell, K-562 with IC50 of 14.27 µg/mL, while chloroform, ethyl acetate and methanol extracts from the stem of the plant inhibited K-562 cells growth with IC50 of 19.50, 24.10 and 85.40 µg/mL respectively. Bioactive chloroform extract of Turraea vogelii leaves affords two triterpenoids: oleana-12,15,20-trien-3ß-ol (1), and oleana-11,13-dien-3ß,16α,28-triol (2), with six fatty esters, ethyl hexaeicos-5-enoate (3), 3-hydroxy-1,2,3-propanetriyltris(tetadecanoate) (4), 1,2,3-propanetriyl(7Z,7'Z,7''Z)tris(-7-hexadecenoate) (5), 1,2,3-propanetriyl(5Z,5'Z,5''Z)tris(-5-hexadecenoate) (6), 1,2,3-propanetriyltris(octadecanoate) (7), and 2ß-hydroxymethyl tetraeicosanoate (8). Tetradecane (9), four fatty acids: hexadecanoic acid (10), tetradecanoic acid (11), (Z)-9-eicosenoic acid (12), and ethyl tetradec-7-enoate (13) were isolated from chloroform extract of Turraea vogelii stem. 1,2,3-propanetriyltris(heptadecanoate) (14), (Z)-9-octadecenoic acid (15) and (Z)-7-tetradecenoic acid (16) were isolated from ethyl acetate extract while (Z)-5-pentadecenoic acid (17) was obtained from methanol extract of the plant stem. Compounds 1, 2, 5, 6, 11, 12, 15, 16 and 17 exhibited pronounced antiproliferative activity against K-562 cell lines.

Flavonoids Isolated from Vitex grandifolia, an Underutilized Vegetable, Exert Monoamine A & B Inhibitory and Anti-inflammatory Effects and Their Structure-activity Relationship.

OBJECTIVES: Vitex grandifolia belongs to family Lamiaceae; it consists of flowering plants and it is also called the mint family. The Yoruba people of southwest Nigeria called it "Oriri" or "Efo oriri". This plant is classified as an underutilized vegetable and little is known about its phytochemistry or its biological evaluations. MATERIALS AND METHODS: Methanol extracts of the dried leaves and stem of the plant were subjected to fractionation and isolation using vacuum layer and column chromatography methods. The structures of the compounds were elucidated using spectroscopic techniques including IR, 1D-, and 2D-NMR and by comparison with the data reported in the literature. They were evaluated in vitro for the inhibition of monoamine recombinant human MAO-A and -B and anti-inflammatory activities. RESULTS: Three known flavonoids were isolated from the methanolic extract of the leaves of V. grandifolia for the first time to the best of our knowledge, i.e. isoorientin (1), orientin (2), and isovitexin (3). Most of the isolated compounds showed selective inhibition of monoamine oxidase B, inhibition of MAO-B by isoorientin (1) and orientin (2) were 9-fold more potent (IC50 (µg/mL) of 11.08 and 11.04) compared to the inhibition of MAO-A (IC50 (µg/mL) of ˃100), while clorgyline and deprenyl were used as positive standards. The isolated flavonoids displayed good activity against the NF-ﭏb assay with IC50 (µg/mL) of 8.9, 12, and 18. This study establishes a link between the structure and the biological activities on the basis of the different patterns of substitution, particularly the C2=C3 double bond and the position of glucose moiety. CONCLUSION: This study is the first to establish the phytochemistry of the polar part of V. grandifolia and the anti-inflammatory and neuroprotective role of these isolated compounds.

Analgesic and anti-inflammatory effects of aqueous extract of Zea mays husk in male Wistar rats.

The analgesic and anti-inflammatory activities of Zea mays husk extract (25, 50, 100, and 200 mg/kg of body weight) were investigated in rats. The hot plate and formalin-induced paw licking models were used to assess analgesic effects of the extract, whereas the carrageenan and cotton pellet models were used for the evaluation of anti-inflammatory activity. The extract at 25, 50, 100, and 200 mg/kg body weight significantly (P < .05) reduced pain stimuli and inflammatory activity when compared with the control group. The reductions in paw licking time and granuloma weight in the formalin and cotton pellet models were both dose dependent. Also, the 200 mg/kg doses of the extract produced higher effects compared with indomethacin (5 mg/kg body of weight) in all the tests. These observations suggest that Z. mays husk extract may have analgesic and anti-inflammatory effects that may be due to its tannins and polyphenolic constituents. These results provide scientific validation for the use of Z. mays husk decoction for the treatment of pain and inflammatory conditions in Nigerian folk medicine.