Letters in Organic Chemistry - Volume 16, Issue 1, 2019

PF-543 has been known as a substance that strongly inhibits SK1. However, it also exhibits antineoplastic activity that is lower than other inhibitors of SK1. In this study, we compared PF-543 and synthesized a newly designed derivative of PF-543 (compound 2) in which two aromatic structures were connected in para-form. The synthesized derivative showed inhibitory effect on SK1, similar to that of PF-543. However, it was more cytotoxic to HT29, AGS, and PC3 cells than PF-543. We also carried out a docking study for SK1 and demonstrated that the synthesized derivative showed interaction with SK1 similar to PF-543. Results obtained from this study suggest that the structure of compound 2 may be well substituted for the structure of PF-543 in terms of biological activity, providing us important structural information for the design of new derivatives of PF-543.

Acetanilide or N-phenylacetamide is an aromatic compound having phenyl ring attached to an acetamido group (–NHCOCH3). In 1886, acetanilide was introduced as an analgesic and antipyretic drug into medical practice by A. Cahn and P. Hepp. Since then, many acetanilide derivatives have been found to have antimicrobial, analgesic, anti-inflammatory, antipyretic, antioxidant, anticonvulsant, anti- cancer, antihyperglycaemic and antimalarial activities. Acetanilide also plays an important role in the synthesis of a number of chemicals as intermediates and precursors. The chief objective of the present article is to highlight the chemistry and pharmacological aspects of various derivatives of acetanilide and their pharmacological activities to assist the future discovery of more efficacious derivatives with less toxicity.

Efficient C-S and C-N cross-coupling reactions have been developed for regioselective, scalable and environmentally benign synthesis of substituted phenothiazine derivatives. Cross-coupling reactions were demonstrated on various challenging substrates using non-toxic, highly economical, readily available ferric citrate as a catalyst to get desired product with high regioselectivity. Atom economy is the added advantage of this protocol since additional N-protection step before coupling and eventual deprotection of the same to obtain the desired product arenot required. To the best of our knowledge, this is the first report on the use of inexpensive ferric citrate as a catalyst without involving any ligand for the synthesis of regioselectively substituted phenothiazine.

Starting from 2,3-dichloroquinoxaline, a synthetic strategy for the preparation of 1-(3- phenylpropyl)-4-(pyridinylmethoxy)[1,2,4]triazolo[4,3-a]quinoxalines is described.

A new phosphonium based coupling reagent DEPO-B has been synthesized from 5- (hydroxyimino)-1,3-dimethylpyrimidine-2,4,6 (1H,3H,5H)-trione (Oxyma B) and diethyl chlorophosphate in presence of base. It is a solid material and the hydrolytic stability and solubility was evaluated for confirming its capability for usage in automated peptide synthesizer.

CDI combined with CH3SO3H was found to be highly effective for the cyclization of 2-aminothiophenol derivatives with carboxylic acids under MW condition. Fourteen benzothiazole derivatives were synthesized in good yield and their structures were characterized by 1H-NMR, 13CNMR, IR and mass spectrometry. This simple, rapid synthetic method is believed to provide a useful process for the synthesis of 2-substituted benzothiazole compounds.

In the present paper, synthesis of few novel pregnane derivatives and their evaluation as potential anti-hyperlipidemic and anti-oxidant agents has been reported. The synthesis of 3β-hydroxy- 16α-methoxy pregn-5-en-20-one (4) was achieved by reaction of 3β-hydroxy-5,16-pregnadiene-20-one (3) with KOH/MeOH under reflux. Compound 4 on treatment with succinic and phthalic anhydride afforded compound 6 and 7, respectively. The reaction of the C-20-oxime-pregnadiene (8) with 1,5- dibromohexane yielded 20-(O-6-bromo hexyl)-oximino-3β-hydroxy-pregn-5, 16-diene (9). A novel heterocyclic derivative 3β-hydroxy-androst-5-en [17,16-c]-2′-methyl-7′ bromo-3′,4′-dihydro quinoline (16) was synthesized by reaction of 3 with 3-bromoaniline. However, attempted synthesis of other heterocyclic derivatives by reaction of (3) with other halogenated amine led to Aza-Michael addition products (10-14). The synthesized compounds were also evaluated for their anti-hyperlipidemic and anti-oxidant activities. Compounds 6 and 14 were found to exhibit more lipid lowering and antioxidant activities in comparison to other compounds.

The present study aimed to investigate the chemical constituents, and antioxidants and antitumor activities of the seagrasses Halodule uninervis and Thalassia hemprichii. Seventeen compounds were isolated from both seagrasses, and identified as flavonoids, phenolic acids, nitrogen compound, steroids and fatty acids. Their structures were established by spectral analysis (UV, MS, and 1D- and 2D-NMR) and chemical investigation (for glycosides). The total metabolites of each seagrass and the isolated flavonoids tested in different in vitro assays (DPPH, ABTS, FRAP, Fe2+ chelating, reducing power, and Ehrlich ascites carcinoma cell line) showed significant antioxidant and antitumor activities. H. uninervis extract revealed good antioxidant activities compared to water and butanol extracts of T. hemprichii, while quercetin 3-O-β-glucoside from H. uninervis revealed potent antioxidant activity at concentration of 25μg/ml. Moreover, the seagrasses extracts were displayed mild antitumor activity against Ehrlich ascites carcinoma cells in mice with less undesirable side effects compared to vincristine as a drug control.

An efficient catalytic synthesis of 4-aryl-3,4-dihydropyrimidine-2(1H)-one derivatives using copper (II), iron (III) and zinc (II) exchanged montmorillonite clays as a catalyst is described. The desired products were obtained in good yields.

In this study, we describe a microwave-based click chemistry method used to prepare a family of novel bis-flavone dimers. The substituted 7-hydroxy and 4’-hydroxy flavonoids were linked through a triazole ring. The compounds were easily synthesized and purified in high yields. The bisflavonoids were tested on different cell lines including HCT116, HepG2, MCF7 and MOLT-4. Several analogues showed to have anticancer activity with IC50 values in the range of 20-60 μM. Flavonoids are known for their anticancer properties and this method provides the basis for new medicinal structures.

Phosphazene bases have been utilized as efficient organocatalysts to catalyze the double Michael additions of divinyl ketones with active methylenes to afford functionalized cyclohexanones in 36-91% yields with >25:1 diastereoselectivity.