Cytotoxic evaluation of new polyhydroxylated steroids from the Red Sea soft coral Litophyton mollis (Macfadyen, 1936).

An efficient column chromatography of the CH2Cl2/MeOH crude extract from the soft coral Litophyton mollis (Macfadyen, 1936) yielded seven steroids, including five 4α-methylated steroids (1-5) and two 19-oxygenated steroids (6-7). Notably, both compounds 3 and 7 are new, identified as (22E)-4α,24-dimethyl-5α-cholesta-22,24(28)-dien-3ß,8ß-diol (3) and (22E,24R)-7ß-acetoxy-24-methyl-cholesta-5,22-dien-3ß,19-diol (7). The chemical structures and relative configurations were elucidated through comprehensive spectroscopic analyses, including 1D and 2D NMR, as well as HRESIMS analysis. The cytotoxicity of metabolites 1-7 was evaluated against three cancer cell lines: MCF-7, HepG2, and NCI-1299. Remarkably, metabolites 6 and 7 exhibited strong cytotoxic activity against MCF-7, with IC50 values of 8.6 and 8.4 µM, respectively, while also showing moderate effects against NCI-1299, with IC50 values of 15.7 and 15.1 µM, respectively. Additionally, steroids 4 and 5 displayed weak cytotoxicity against all three cell lines, with IC50 values in the ranges of 34.7-37.5 and 30.8-46.3 µM, respectively.

New Cytotoxic Monoalkyl Glycerol Ether from the Red Sea Soft Coral Nephthea mollis.

A new monoalkyl glycerol ether, 3-(n-henicosyloxy)propane-1,2-diol (1), was isolated from the CH2 Cl2 /MeOH crude extract of the Red Sea soft coral Nephthea mollis. Additionally, three known related analogs were identified: chimyl alcohol (2), batyl alcohol (3), and 3-(icosyloxy)propane-1,2-diol (4). The chemical structure of 3-(n-henicosyloxy)propane-1,2-diol was determined using advanced spectroscopic analyses, including 1D, 2D Nuclear Magnetic Resonance (NMR), Electron Ionization mass spectra (EI-MS), and High-Resolution Electron Spray Ionization mass spectra (HR-ESI-MS) analyses. Furthermore, the identification of chimyl alcohol, batyl alcohol and 3-(icosyloxy)propane-1,2-diol was achieved by studying their EI mass fragmentation analyses and comparing their mass data with those previously reported in the literature. The cytotoxic activity of the Nephthea mollis crude extract and 3-(n-henicosyloxy)propane-1,2-diol was evaluated against five human cancer cell lines: HepG2 (hepatocellular carcinoma), MCF-7 (breast carcinoma), NCI-1299 (lung carcinoma), HeLa (cervical cancer cell), and HT-29 (colon adenocarcinoma). Moreover, 3-(n-henicosyloxy)propane-1,2-diol revealed moderate cytotoxicity against the HeLa cell lines with an IC50 value of 24.1 µM, while showing inactivity against the remaining cell lines (IC50 >100 µM).

Cytotoxic and anti-bacterial evaluation of two new aromatic A-ring steroids isolated from the Red Sea soft coral Dendronephthya spp.

A successful column chromatography of a CHCl3/MeOH crude extract of Dendronephthya spp. soft coral led to the isolation of two new aromatic A-ring steroids (1-2), together with three known compounds (3-5). Both 1 and 2 are 19-norsteroids. The chemical structures were elucidated based on extensive 1D, 2D NMR, and EIMS analyses. In cytotoxic bioassays, compounds 1-5 were tested against three cancer cell lines: MCF-7, NCI-1299, and HepG2, with IC50 in the ranges of 22.1-85.4, 26.9-88.7, and 25.9-93.7 µM, respectively. Compounds 1, 2, and 5 showed moderate degrees of inhibition against Escherichia coli and Pseudomonas sp. at 100 and 150 µg/mL, while exhibiting weak inhibition against Bacillus cereus and Staphylococcus aureus at 150 µg/mL.

Glycine protects against doxorubicin-induced heart toxicity in mice.

Doxorubicin (DOXO) is a well-known cancer chemotherapeutic. However, its toxic effect on the heart limits its clinical application. This study aimed to assess the effectiveness of glycine administration to counteract the DOXO-induction of cardiomyopathy in mice. Fifty male albino mice were divided into five groups (n = 10/group) as follows: control, DOXO, Gp100, Gp150, and Gp200. Histopathological examination of the heart, and biochemical examinations for heart function (creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)), inflammation (tumor necrosis factor-alpha (TNF-α) and interleukin 10 (IL-10)), oxidative stress (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase, nitric oxide (NO), and uric acid), kidney function (urea and creatinine), and minerals (calcium, phosphorus, sodium, and potassium) were carried out. Cardiomyopathy induced by DOXO treatment (15 mg/kg total dose) was ascertained via pathological alterations seen in heart tissue and verified biochemically via increases (P < 0.001) in CPK, LDH, AST, TNF-α, IL-10, MDA, NO, Na, and K levels along with decreases (P < 0.001) in GSH, SOD, catalase, and uric acid. Glycine co-treatment, using doses of 100, 150, and 200 mg/kg, in a dose-dependent manner, displayed ameliorated heart architecture, significantly (P < 0.001) improved biochemical heart function tests, reduced oxidative stress and inflammation, and controlled mineral levels. The positive actions of glycine in DOXO-induced cardiotoxicity amelioration via modulating oxidative stress, inflammation, and immunity are confirmed. Glycine antioxidative properties may be behind its positive outcomes. Finally, we present glycine as a worthy possible option against DOXO-induced heart damage after more validation.

A Newly Synthesized Derivative and a Natural Parent Molecule: Which Would Be More Beneficial as a Future Antitumor Candidate? Docking and In Vivo Study.

Seeking for new effectual anticancer drugs is of great importance. In this study, a newly synthesized and well-characterized chromene derivative (ethyl 2-amino-4-phenyl-4H-benzo(h)chromene-3-carboxylate) "C" was prepared. Molecular docking studies were done. The new compound "C" in compare to the natural parent Quercetin "Q," as a well-known natural chromene derivative with antioxidant and antitumor activities, were tested for their antitumor activity against Ehrlich ascites carcinoma (EAC)-bearing mice. Both reduced ascites volume, decreased viable EAC cells, and prolonged EAC-bearing mice life span. They normalized troponin, creatine kinase-MB, lactate dehydrogenase, and urea levels, reversed liver enzyme activities towards normal, and increased antioxidant levels while reduced tumor necrosis factor-alpha (TNF-α) levels. Compared to each other, the new synthetic derivative "C" showed stronger antineoplastic effects than the natural parent "Q" may via the anti-inflammatory activities. Therefore, the newly synthesized chromene derivative is more promising as a future antitumor candidate than the natural parent molecule "Quercetin." Finally, our results encourage researchers to pay more attention to developing more novel natural-based derivatives that would be more beneficial as future therapeutics than their natural parents.

Utilization of N-acyl compounds for the synthesis of tricyclic and bridged heterocyclic compounds.

N-acyl derivative 4 was prepared via the reaction of methyl anthranilate with ethyl bromoacetate then refluxing the formed amino ester 3 with acetic anhydride. Cyclization of 4 in presences of sodium methoxide and methanol forming 2,4-pyrrolidindione derivative 5. 2,4-Quinolidinone 6 was obtained via cyclization of 4 in dry toluene and sodium hydride. On the other hand, indolinone derivative 8 was obtained by cyclization of 4 in toluene and free from alcohol due to retro Diekmann-condensation. On treatment of 8 with sodium hydride, refluxing toluene and in presences of Crown ether gave tricyclic compound 9. Also, treatment of 2-pyrrolidinone with trimethylene chlorobromide produced 10 which cyclized using base and solvent to the bridged ring derivatives 11. The acidic hydrolysis of 11 afforded the corresponding amino acid 13. Whereas derivative 14 was obtained by the reaction of 2-pyrrolidinone with ethyl 3-bromopropionate which on cyclization gave azabicyclo[3,2,1]octan-4,8-dione derivative 15. Compound 15 underwent acidic hydrolysis to the amino ketone derivative azepanone hydrochloride 17.