Abdulmumeen A. Hamid

Synthesis of novel anticancer agents through opening of spiroacetal ring of diosgenin.

Diosgenin has been modified to furostane derivatives after opening the F-spiroacetal ring. The aldehyde group at C26 in derivative 8 was unexpectedly transformed to the ketone 9. The structure of ketone 9 was confirmed by spectroscopy and finally by X-ray crystallography. Five of the diosgenin derivatives showed significant anticancer activity against human cancer cell lines. The most potent molecule of this series i.e. compound 7, inhibited cellular growth by arresting the population at G0/G1 phase of cell division cycle. Cells undergo apoptosis after exposure to the derivative 7 which was evident by increase in sub G0 population in cell cycle analysis. Docking experiments showed caspase-3 and caspase-9 as possible molecular targets for these compounds. This was further validated by cleavage of PARP, a caspase target in apoptotic pathway. Compound 7 was found non-toxic up to 1000mg/kg dose in acute oral toxicity in Swiss albino mice.

(22β,25R)-3β-Hydroxy-spirost-5-en-7-iminoxy-heptanoic acid exhibits anti-prostate cancer activity through caspase pathway

&NA; Prostate cancer is one of the most common cancers in men. Diosgenin and related compounds are potential cytotoxic agents. Twelve diverse analogues of long chain fatty acid/ester of diosgenin‐7‐ketoxime have been prepared. Six of the analogues exhibited significant anticancer activity against a panel of human cancer cell lines with IC50 ranging from 12 to 35 &mgr;M. Compound 16, the best representative of the series exerted S phase arrest in DU145 prostate cancer cells and induced apoptosis through caspase pathway. Additionally, these analogues inhibited lipopolysaccharide induced pro‐inflammatory cytokines (TNF‐&agr; and IL‐6) up to 47.7% and 23.3% respectively. Compound 16 was found to be safe in acute oral toxicity in Swiss albino mice up to 300 mg/kg dose. The anticancer and antiinflammatory properties of compound 16 are important and can further be optimized for a better anti‐prostate cancer candidate. Graphical abstract Figure. No caption available. HighlightsDiverse long chain fatty acid/esters of diosgenin‐7‐ketoxime have been prepared.Analogue 16, cytotoxicity IC50 = 12 &mgr;M prostate cancer, cell cycle arrest at S phase and induces apoptosis through caspase pathway.Simultaneously antiinflammatory property by inhibition of TNF‐&agr; and IL‐6.Safe up to 1000 mg/kg dose in Swiss‐albino mice.Simultaneous, antiinflammatory property in an anticancer molecule is favourable.

Isolation and antiproliferative activity of chemical constituents from Asystasia buettneri Lindau

Abstract N-hexane and methanol extracts of Asystasia buettneri Lindau aerial parts exhibited antiproliferative activity on leukaemia blood carcinoma, K-562. Hexadecane (1), 1,3-propan-2-ol (9Z,12′Z,15″Z)-bis(doeicos-9,12,15-trienoate) (2), hydrocarbon, 2,3,3,10,23-pentamethyl tetraeicos-10,13,16-trien-1-ol (3), hexadecanoic acid (4) and taraxerol (5) were isolated from n-hexane extract; stigmasterol (6) and (Z)-9-octadecenoic acid (7) were isolated from ethyl acetate extract; while unsaturated hydrocarbons, octadecene (8), 8-methyl tetradec-6-ene (9) and 19-methyl eicos-1-ene (10), fatty acids, (Z)-5-hexadecenoic acid (11), 11,22-dimethyl ethyltrieicos-11-enoate (12) and taraxasterol (13) were isolated from methanol extract of the plant. Compounds 4, 5, 7, 11, 12 and 13 exhibited antiproliferative activity against K-562, while compounds 5, 6, 7 and 9 revealed antiproliferative activity by inhibiting hepatic liver (WRL68) cell lines.

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

Abstract 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-3β-ol (1), and oleana-11,13-dien-3β,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 2β-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.

Isolation, characterization and antiproliferative evaluation of constituents from stem extracts of Alafia barteri Oliv. Hook. F.

This study was to investigate the constituents of stem extracts of Alafia barteri and evaluate its antiproliferative activity in order to support its ethnomedicinal application. Chromatographic isolation procedure was used to separate the constituents from n-hexane, ethyl acetate, and methanol extracts of Alafia barteri stem and testing against three human cancer cell lines, i.e., leukemia carcinoma, K-562, hepatic liver cancer cells, WRL68, and breast carcinoma, MCF-7 using the MTT assay. Thirteen known fatty esters: 1,2,3-propanetriyl tris(dodecanoate) (1), 1,2,3-propanetriyl tris(tetradecanoate) (2), 1,2,3-propanetriyl tris(pentadecanoate) (3), 1,2,3-propanetriyl (5Z,5′Z,5″Z)tris(-5-pentadecenoate) (4), 1,2,3-propanetriyl (7Z,7′Z,7″Z)tris(-7-pentadecenoate) (5), 1,2,3-propanetriyl tris(hexadecanoate) (6), 1,2,3-propanetriyl (9Z,9′Z,9″Z)tris(-9-hexadecenoate) (7), 1,2,3-propanetriyl (9Z,9′Z,9″Z)tris(-9-octadecenoate) (8), methyl octanoate (9), 9Z-ethyloctadec-9-enoate (10), 1,2,3-propanetriyl (5Z,5′Z,5″Z)tris(-5-eicosenoate) (11), dodec-5-enoic acid (12) and 1,2,3-propanetriyl (9Z,12′Z,15″Z)tris(-9,12,15-uneicostrienoate) (13); an isoalcohol, 12-methyltridecan-2-ol (14), β-sitosterol (15), lupeol (16), and α-amyrin (17) were isolated from the extracts and characterized using infrared, nuclear magnetic resonance, and mass spectroscopic techniques. Compounds 2 and 3 showed cytotoxic activity against WRL68 cell lines (IC50 = 63.50 and 65.03 µM, respectively), while 5 exhibited cytotoxic activity against MCF-7 (IC50 = 85.26 µM). Compounds 9, 12, and 16 inhibited the growth of K-562 carcinoma with IC50 of 28.31, 52.32, and 85.20 µM, respectively. The phytochemical constituents of Alafia barteri stem extracts could be considered as lead compounds for further investigation as antiproliferative agents.Graphical abstractAntiproliferative activity………WRL68 Compounds 2 and 3: IC50 = 63.50 ± 7.07 × 10−3 and 65.03 ± 7.07 × 10−3 µM. MCF-7 Compound 5: IC50 = 85.26 ± 1.41 × 10−2 µM.

Correction to: Isolation, characterization and antiproliferative evaluation of constituents from stem extracts of Alafia barteri Oliv. Hook. F.

Correction to: https://doi.org/10.1007/s00044-017-2033-4

Triterpenoids from the Aerial Parts of Smilax kraussiana as Antitumor Agents

Smilax kraussiana Meisn. (Synonym Smilax korthalsii A. DC.) is an ornamental plant. It is an evergreen shrub with climbing branches, stapler tendrils, and thorny flowers [1–9]. It is commonly known as West African sarsaparilla. Traditionally it is known as Odufat by the Ibibios, Uruk–ekwong by the Efiks, Jiabanammuo by the Ibos, Kurangawofi by the Hausas, and Ekanamagbo/Egun-igbao by the Yoruba of Nigeria. Preliminary work on the root of the plant revealed that it contained saponins, tannins, simple sugars, cardiac glycosides, and flavonoids [10]. The plant is used in the treatment of tumors, infertility, inflammatory rheumatism, gout, kidney problems, gonorrhea and syphilis, fever, malaria, and skin diseases [1, 4, 5, 11–13]. Some of the therapeutic properties of the plant have been established by various researchers. The acute toxicity potential of the plant and its antiplasmodial, antipyretic, anti-inflammatory, contraceptive, as well as analgesic activities, have been reported [10, 14–16]. However, only the cytotoxicity and phytochemistry of the ethyl acetate extract of the plant leaves have been reported [17]. In this study, we report five compounds, octadecane (1), dodec-1-ene (2), 3 -acetyl-23,24-dihydroxyolean-5ene (3), ursa-12,20-dien-19 -ol-3-one (4), and oleana-9(11),12-dien-3-ol (5) isolated from chloroform extract, and another five compounds, 1,2,3-propanetriyl (7Z,7 Z,7 Z)tris(-7-tetradecenoate) (6), campesterol (7), cis-hexadec-9-enoic acid (8), Z-7,10,13,16,19-heptaeicosa-pentaenoic acid (9), and (Z)-5,8-eicosadienoic acid (10) isolated from the methanol extract of aerial parts of Smilax kraussiana (S. kraussiana). Furthermore, the antiproliferative activity of the isolates was discussed to support its traditional medicinal applications.

New Triterpenoids from the Leaves of Alafia barteri

A new oleanane derivative, 3β-acetyloleana-5,12-dien-2,23-diol (1), and a new lupane compound, lup-11,20(29)-dien-3 β,28-diol (2), together with eight known compounds, oleana-5,12-dien-3β-yl acetate (3), lup-5,20(29)-dien-3 β -yl acetate (4), 18-methylethylnonadecan-19-oic-9-enoate (6), octadecane (5), cis-pentadec-7-enoic acid (7), cis-tetradec-7,10-dienoic acid (8), cholest-4-en-3-one (9), and stigmasterol (10), were isolated from the leaves of Alafia barteri. Their structures were elucidated by IR, 1D and 2D NMR, and mass spectroscopy. Compounds 7 and 8 exhibited cytotoxic activities against K562, WRL, and MCF-7 tumor cell lines with IC50 in the range of 8.80 to 37.10 μg/mL, while compounds 2 and 9 suppressed the viability of K562 cells with IC50 of 120.2 and 14.48 μg/mL. Compounds 1, 3, and 4 showed low cytotoxic properties on the tested cell lines.