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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Khalifa, Shaden A. M., et al.
(författare)
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Marine Natural Products : A Source of Novel Anticancer Drugs
- 2019
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Ingår i: Marine Drugs. - : MDPI AG. - 1660-3397. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- Cancer remains one of the most lethal diseases worldwide. There is an urgent need for new drugs with novel modes of action and thus considerable research has been conducted for new anticancer drugs from natural sources, especially plants, microbes and marine organisms. Marine populations represent reservoirs of novel bioactive metabolites with diverse groups of chemical structures. This review highlights the impact of marine organisms, with particular emphasis on marine plants, algae, bacteria, actinomycetes, fungi, sponges and soft corals. Anti-cancer effects of marine natural products in in vitro and in vivo studies were first introduced; their activity in the prevention of tumor formation and the related compound-induced apoptosis and cytotoxicities were tackled. The possible molecular mechanisms behind the biological effects are also presented. The review highlights the diversity of marine organisms, novel chemical structures, and chemical property space. Finally, therapeutic strategies and the present use of marine-derived components, its future direction and limitations are discussed.
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| 3. |
- Shahzad, Danish, et al.
(författare)
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Novel C-2 Symmetric Molecules as -Glucosidase and -Amylase Inhibitors : Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
- 2019
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:8
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Tidskriftsartikel (refereegranskat)abstract
- A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a-5h, have been synthesized, characterized by H-1-NMR and C-13-NMR, and evaluated for their in vitro -glucosidase and -amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound 5g was the most potent derivative in the series, and powerfully inhibited both -glucosidase and -amylase. The IC50 of 5g against -glucosidase was 0.35917 +/- 0.0189 mu M (standard acarbose IC50 = 6.109 +/- 0.329 mu M), and the IC50 value of 5g against -amylase was 0.4379 +/- 0.0423 mu M (standard acarbose IC50 = 33.178 +/- 2.392 mu M). The Lineweaver-Burk plot indicated that compound 5g is a competitive inhibitor of -glucosidase. The binding interactions of the most active analogues were confirmed through molecular docking studies. Docking studies showed that 5g interacts with the residues Trp690, Asp548, Arg425, and Glu426, which form hydrogen bonds to 5g with distances of 2.05, 2.20, 2.10 and 2.18 angstrom, respectively. All compounds showed high mutagenic and tumorigenic behaviors, and only 5e showed irritant properties. In addition, all the derivatives showed good antioxidant activities. The pharmacokinetic evaluation also revealed promising results
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| 4. |
- Ujan, Rabail, et al.
(författare)
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Drug-1,3,4-Thiadiazole Conjugates as Novel Mixed-Type Inhibitors of Acetylcholinesterase : Synthesis, Molecular Docking, Pharmacokinetics, and ADMET Evaluation
- 2019
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:5
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Tidskriftsartikel (refereegranskat)abstract
- A small library of new drug-1,3,4-thiazidazole hybrid compounds (3a-3i) was synthesized, characterized, and assessed for their acetyl cholinesterase enzyme (AChE) inhibitory and free radical scavenging activities. The newly synthesized derivatives showed promising activities against AChE, especially compound 3b (IC50 18.1 +/- 0.9 nM), which was the most promising molecule in the series, and was substantially more active than the reference drug (neostigmine methyl sulfate; IC50 2186.5 +/- 98.0 nM). Kinetic studies were performed to elucidate the mode of inhibition of the enzyme, and the compounds showed mixed-type mechanisms for inhibiting AChE. The Ki of 3b (0.0031 mu M) indicates that it can be very effective, even at low concentrations. Compounds 3a-3i all complied with Lipinski's Rule of Five, and showed high drug-likeness scores. The pharmacokinetic parameters revealed notable lead-like properties with insignificant liver and skin-penetrating effects. The structure-activity relationship (SAR) analysis indicated pi-pi interactions with key amino acid residues related to Tyr124, Trp286, and Tyr341.
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| 5. |
- Zahra, Maram Hussein, et al.
(författare)
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Alpinia zerumbet (Pers.) : Food and Medicinal Plant with Potential In Vitro and In Vivo Anti-Cancer Activities
- 2019
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 24:13
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers. Methods: The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model. Results: A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, H-1-NMR and C-13-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 mu g/mL, respectively. Conclusion: Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet.
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