Pentacyclic Derivatives Research Articles

Synthesis, Identifications and Study Inhibitory anti-Cancer Activity for Some New Heterocyclic Compounds from Derivatives Coumarine

In this research paper, our work included the synthesis of some new heterocyclic organic derivatives compounds {penta, hexa, hepta, and octa} rings membered by using Schiff Base reaction methods. These cyclic derivatives have given good results, in anti-cancer Activity, and can be prepared there are compounds in three steps. First step:-\ It involves the preparation of some heterocyclic penta-cyclic derivatives; it is contained from Imidazolidine (five ring members). Second step:-\ It includes the preparation of some new heterocyclic hepta and octa derivate containing from 1, 3- Oxazepine and Oxazapane (hepta and octa ring saturated and unsaturated members) Third step:-\ involved the study inhibitory of activity anticancer of some compounds synthesis from this line. The compounds were analyzed and characterized using spectrum photometers by {FT-IR, 1HNMR}

Novel pentacyclic derivatives and benzylidenes of the progesterone series cause anti-estrogenic and antiproliferative effects and induce apoptosis in breast cancer cells.

The promising antitumor effects of progesterone derivatives have been identified in many studies. However, the specific mechanism of action of this class of compounds has not been fully described. Therefore, in this study, we investigated the antiproliferative and (anti)estrogenic activities of novel pentacyclic derivatives and benzylidenes of the progesterone series. The antiproliferative effects of the compounds were evaluated on hormone-dependent MCF7 breast cancer cells using the MTT test. Estrogen receptor α(ERα) activity was assessed by a luciferase-based reporter assay. Immunoblotting was used to evaluate the expression of signaling proteins. All benzylidenes demonstrated inhibitory effects with IC50 values below 10 µM, whereas pentacyclic derivatives were less active. These patterns may be associated with the lability of the geometry of benzylidene molecules, which contributes to an increase in the affinity of interaction with the receptor. The selected compounds showed significant anti-estrogenic potency. Benzylidene 1d ((8S,9S,10R,13S,14S,17S)-17-[(2E)-3-(4-fluorophenyl)prop-2-enoyl]-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthren-3-one) was the most active in antiproliferative and anti-estrogenic assays. Apoptosis induced by compound 1d was accompanied by decreases in CDK4, ERα, and Cyclin D1 expression. Compounds 1d and 3d were characterized by high inhibitory potency against resistant breast cancer cells. Apoptosis induced by the leader compounds was confirmed by PARP cleavage and flow cytometry analysis. Compound 3d caused cell arrest in the G2/M phase. Further analysis of novel derivatives of the progesterone series is of great importance for medicinal chemistry, drug design, and oncology.

Synthesis of spiro-annulated cyclobutane derivatives through ketene [2+2] cycloaddition and ring-rearrangement metathesis

Herein is reported a concise synthesis of spiro-annulated cyclobutane tetracyclic and pentacyclic derivatives by ketene addition, and ring-rearrangement metathesis (RRM) as key steps, starting with commercially available norbornadiene and dicyclopentadiene. The tetracyclic spiro-derivative contains a [5/5/4] core unit, which is the key building block to angular triquinanes synthesis. Whereas, the pentacyclic spiro-derivative contains a basic core skeleton of presilphiperfolanes, and other sesquiterpenoids.

Base-Dependent Divergent Annulation of 4-Chloro-3-formylcoumarin and Tetrahydroisoquinoline: Application to the Synthesis of Isolamellarins and Hydroxypyrrolones.

A series of pyrrolo[2,1- a]isoquinoline and coumarin-fused pentacyclic derivatives were synthesized via base-mediated divergent annulation of 4-chloro-3-formylcoumarin and tetrahydroisoquinoline as a key step. This method was then extended to the preparation of isolamellarins A and B (isolamellarin G trimethyl ether). When exposed to UV light, the pyrrolo[2,1- a]isoquinoline- and coumarin-fused pentacycles B were found to undergo aerobic oxidation to give the corresponding hydroxypyrrolones.

Reaction of Methyl (2-Methylidene)-3-oxolup-20(29)-en-28-oate with Dimethyl Trimethylsilyl Phosphite

A method of phosphorylation of pentacyclic triterpenoids derivatives containing an α,β-unsaturated carbonyl fragment in the ring A was described by the example of the reaction of methyl (2-methylidene)-3-oxolup-20(29)-en-28-oate with dimethyl trimethylsilyl phosphite. Methyl 2-dimethoxyphosphorylmethyl-3-oxolup-20(29)-en-28-oate was obtained as two epimers in a 2: 1 ratio in a 70% yield.

Synthesis of Cyclopenta[4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidine Derivatives. Dimroth Rearrangement of Triazolopyrimidines

Methods of the preparation of 9- (methylsulfanyl)cyclopenta[4',5']pyrido[3',2':4,5]thieno[3,2-d]- pyrimidines and pentacyclic triazolopyrimidines derivatives were developed. The Dimroth rearrangement of these compounds was studied.

New furan fused 1,10-phenanthroline pentacyclic derivatives: Synthesis and photophysical properties

Two new donor-acceptor-donor (D-A-D) small molecules, named L1 and L2, based on furan-fused and fluorinated furan-fused 1,10-phenanthroline as electron-acceptor units and 4-(bis(4-methoxyphenyl)amino)phenyl as electron-donor units, were designed and synthesized. The photophysical and electrochemical properties were studied. The results are compared and discussed with respect to the influence of attached fluorine and solvent polarity. L1 and L2 emit intense blue light in non-polar solvent with high photoluminescence (PL) quantum yield (ηPL) of 1 for L2. The absorption and PL spectra of L2 with attached fluorine atoms are red-shifted compared with those of L1. Red shifts of PL maxima are observed with the increasing solvent polarity in solution spectra for both L1 and L2. ηPL values in solutions decrease as solvent polarity increases and the ηPL difference for L1 and L2 in solution is not so pronounced as for L1 and L2 thin films. In addition, the effect of protonation on the nitrogen atoms of phenanthroline in thin films is shown. L1 and L2 were tested in the light-emitting devices and their electroluminescent properties are also reported. The preliminary results show L1 and L2 are almost pure white emitter and greenish blue emitter, respectively.

Antiproliferative activity of amino substituted benzo[b]thieno[2,3-b]pyrido[1,2-a]benzimidazoles explored by 2D and 3D cell culture system

Benzimidazo[1,2-a]quinolines and benzo[b]thieno[2,3-b]pyrido[1,2-a]benzimidazoles with amino chains on the different positions have been evaluated by 2D and 3D assays on the human breast cancer cells. Pentacyclic derivatives were synthesized by microwave assisted amination to study the influence of the thiophene substructure on antitumor activity in comparison to tetracyclic analogues. The results obtained from 2D assay reveals that the antitumor activity is strongly dependent on the nature and position of amino chains. Tetracyclic derivatives displayed selective activity on SK-BR-3 with the 2-amino substituted derivatives as the most active ones while pentacyclic derivatives 6–16 and 21–25 showed more pronounced activity on T-47D. The evaluation of antitumor activity in the 3D assay pointed out that some of the tetracyclic and pentacyclic amino substituted derivatives showed selective activity on the MDA-MB-231 cell line.Influence of physico-chemical properties of the compounds on antiproliferative activity have been investigated by multivariate statistical methods. As a measure of lipophilicity, experimental Chrom LogD values have been determined and number of structural parameters have been calculated for investigated compounds. Main factors contributing to the antiproliferative effect for both 2D and 3D cell cultures are found to be basicity, lipophilicity, molecular weight and number of H-bond donors.

Stereoisomeric Composition of Natural Myrtucommulone A.

Myrtucommulone A (MC A) (1), isolated from Myrtus communis (myrtle), shows the same pharmacological activity for inhibition of inflammation and induction of apoptosis as synthetic MC A, which consists of three stereoisomers, i.e., two enantiomers and one meso form. This led to the question of whether the natural MC A is a pure stereoisomer or a mixture of stereoisomers. The specific rotation and electronic circular dichroism (ECD) data of natural MC A (1) as well as of a pentacyclic derivative 4 revealed that naturally occurring MC A (1) consists of the racemate and the meso form in a 1:1 ratio. A probable precursor of MC A (1), nor-semimyrtucommulone (5), was also isolated from myrtle as a racemate. The absolute configurations of the enantiomers of 1 and 5 were determined using a combination of experimental and quantum-chemical calculated ECD spectra.

Biogenic polycyclic aromatic hydrocarbons in sediments of the San Joaquin River in California (USA), and current paradigms on their formation.

Biogenic perylene and higher plant pentacyclic triterpenoid-derived alkylated and partially aromatized tetra- and pentacyclic derivatives of chrysene (3,4,7-trimethyl- and 3,3,7-trimethyl-1,2,3,4-tetrahydrochrysene, THC) and picene (1,2,9-trimethyl- and 2,2,9-trimethyl-1,2,3,4-tetrahydropicene, THP) were two- to four-fold more abundant than pyrogenic PAH in two sediment cores from the San Joaquin River in Northern California (USA). In a core from Venice Cut (VC), located in the river, PAH concentrations varied little downcore and the whole-core PAH concentration (biogenics + pyrogenics) was 250.6 ± 73.7ngg(-1) dw; biogenic PAH constituted 67 ± 4% of total PAH. THC were 26 ± 9% of total biogenic PAH, THP were 36 ± 7%, and perylene was 38 ± 7%. PAH distributions in a core from Franks Tract (FT), a former wetland that was converted to an agricultural tract in the late 1800s and flooded in 1938, were more variable. Surface sediments were dominated by pyrogenic PAH so that biogenic PAH were only ~30% of total PAH. Deeper in the core, biogenic PAH constituted 60-93% of total PAH; THC, THP and perylene were 31 ± 28%, 24 ± 32%, and 45 ± 36% of biogenic PAH. At 100-103cm depth, THP constituted 80% of biogenic PAH and at 120-123cm perylene was 95% of biogenic PAH. Current concepts related to precursors and transformation processes responsible for the diagenetic generation of perylene and triterpenoid-derived PAH are discussed. Distributions of biogenic PAH in VC and FT sediments suggest that they may not form diagenetically within these sediments but rather might be delivered pre-formed from the river's watershed.

Biarylmethane and Fused Heterocyclic Arene Synthesis via in Situ Generated o- and/or p-Naphthoquinone Methides.

o- and/or p-naphthoquinone methides (NQMs) can be selectively prepared by the ring opening of 1-(siloxymethyl)-1,4-epoxy-1,4-dihydronaphthalene derivatives based on a substituent effect at the 4 position of the substrates. The 4-alkyl- or silyl-substituted 1-(siloxymethyl)-1,4-epoxy-1,4-dihydronaphthalene was transformed to o-NQM (1-naphthoquinone-2-methide), which underwent Friedel-Crafts 1,4-addition of the α,β-unsaturated carbonyl moiety to provide the 2-benzyl-1-naphthol as the biarylmethane and [4 + 2]-cycloaddition with a dienophile to give the fused heterocyclic arene. Meanwhile, the 4-unsubstituted 1-(siloxymethyl)-1,4-epoxy-1,4-dihydronaphthalene could be converted to the corresponding 4-benzyl-1-naphthol by the Friedel-Crafts 1,6-addition of p-NQM (1-naphthoquinone-4-methide) generated by the site-selective ring opening of the 1,4-epoxy moiety. Furthermore, the 4-(siloxymethyl)-(1,4-bis(siloxymethyl))-1,4-epoxy-1,4-dihydronaphthalene was transformed into a 2,4-bisbenzyl-1-naphthol or pentacyclic derivative via both the o- and p-NQM intermediates.

Discovery of butyrylcholinesterase inhibitors among derivatives of azaphenothiazines

The study presents the discovery of novel butyrylcholinesterase (BuChE) inhibitors among derivatives of azaphenothiazines by application of in silico and in vitro screening methods. From an in-house library of compounds, 143 heterocyclic molecules derived from the azaphenothiazine scaffold were chosen for virtual screening. Based on results of the docking procedure, 15 compounds were identified as exhibiting the best fit for the two screening complexes (ligand – AChE and ligand – BuChE). Five compounds displayed moderate AChE and good BuChE inhibitory activity at screening concentrations of 10 µM. The IC50 values for active BuChE inhibitors were in the 11.8–122.2 nM range. Three of the most active inhibitors are tetra- or pentacyclic derivatives of azaphenothiazines with the same N-methyl-2-piperidinethyl substituent.

Synthetic pathway to 22,23-dioxocholestanic chain derivatives and their usefulness for obtaining brassinosteroid analogues

Recognizing the functionality of the pentacyclic steroidal derivative 7a as important synthon to obtain new brassinosteroid analogs, we have accomplished the derivatization of hecogenin, a sapogenin from the 25R serie containing a carbonyl group at C-12, to a 22,23-dioxocholestanic chain derivative. Starting from hecogenin acetate (5a) or hecogenin tosylate (5b), we obtained two pentacyclic derivatives (7a and 7b) which were subjected to an oxidation reaction on the double bond at C-12(23) to obtain a 22,23-dioxocholestanic chain, with the regeneration of the carbonyl group at C-12. Reduction of the carbonyl groups lead to the 20-epi-12,23-dihydroxy-22-oxo system 11a–b. The absolute configuration of compound 11a was established by X-ray diffraction analysis.

ChemInform Abstract: Facile Construction of [6,6]‐, [6,7]‐, [6,8]‐, and [6,9]Ring‐Fused Triazole Frameworks by Copper‐Catalyzed, Tandem, One‐Pot, Click and Intramolecular Arylation Reactions: Elaboration to Fused Pentacyclic Derivatives.

AbstractThe copper‐catalyzed click reaction of O‐alkynyl‐iodophenols with benzyl‐ or arylazides affords the triazole ring which is subsequently arylated to provide the title tricycles (36 examples).

ChemInform Abstract: Expedient Approach for the Synthesis of Novel Indenothiophene Derivatives.

AbstractAll products are isolated by simple work‐up and purified by recrystallization.

Facile Construction of [6,6]‐, [6,7]‐, [6,8]‐, and [6,9]Ring‐Fused Triazole Frameworks by Copper‐Catalyzed, Tandem, One‐Pot, Click and Intramolecular Arylation Reactions: Elaboration to Fused Pentacyclic Derivatives

AbstractA sequential copper‐catalyzed, one‐pot, click reaction–intramolecular direct arylation, which involves two mechanistically distinct reactions (atom‐economical click reaction and direct arylation of 1,2,3‐triazole), to generate [6,6]‐, [6,7]‐, [6,8]‐, and [6,9]ring‐fused triazoles is reported. Furthermore, a unique divergence of reactivity between the fused triazoles prepared from 2‐bromobenzyl azide and 2‐bromophenylazide that leads to a fused pentacyclic heterocycle for the former and a C–C‐coupled, biphenyl‐fused, tricyclic product for the latter is observed under Pd catalysis. All of the key products have been characterized by single‐crystal X‐ray crystallography.

ChemInform Abstract: CuCl2‐Promoted 6‐endo‐dig Chlorocyclization and Oxidative Aromatization Cascade: Efficient Construction of 1‐Azaanthraquinones from N‐Propargylaminoquinones.

AbstractTetra‐ and pentacyclic derivatives (IV) and (XII) provide building blocks of acridine alkaloids.

Phenothiazinium photosensitisers IX. Tetra- and pentacyclic derivatives as photoantimicrobial agents

Methylene blue derivatives, synthesised as novel photosensitising agents are usually simple auxochromic variations on the lead compound. The current paper represents the initial report on the synthesis and biological testing of a new class of phenothiazinium derivatives, having either one or two tetrahydropyridine rings fused to the phenothiazinium chromophore. The derivatives exhibited extended absorption wavelengths, increased amphiphilic character and much greater photoantimicrobial efficacies compared to methylene blue, some examples being more effective even than dimethyl methylene blue. The high activities of this class of photosensitiser recommend its use in infection control, both locally and in blood product decontamination.

A novel quinone‐based derivative (DTNQ‐Pro) induces apoptotic death via modulation of heat shock protein expression in Caco‐2 cells

The resistance of human colon adenocarcinoma cells to antineoplastic agents may be related to the high endogenous expression of stress proteins, including the family of heat shock proteins (HSPs). Recently, a quinone-based pentacyclic derivative, DTNQ-Pro, showed high cytotoxic activity in human colon carcinoma cell lines. The aim of the present study was to determine the precise cellular mechanisms of this cytotoxic action of DTNQ-Pro. Using human colorectal carcinoma-derived Caco-2 cells as a model, we studied the effects of DTNQ-Pro on cellular viability and oxidative stress; HSP70 and HSP27 accumulation; and cell cycle, differentiation and apoptosis. Incubation of Caco-2 cells with DTNQ-Pro reduced cell growth and increased the levels of reactive oxygen species in mitochondria. After 48 h of treatment, cells surviving showed an increased expression of Mn-superoxide dismutase (SOD), nitric oxide production and membrane lipid peroxidation. Treatment with DTNQ-Pro decreased HSP70 expression, and redistributed HSP27 and vimentin within the cell. DTNQ-Pro down-regulated the expression of A and B cyclins with arrest of the cell cycle in S phase and increased cellular differentiation. A second treatment of Caco-2 cells with DTNQ-Pro induced cellular death by activation of the apoptotic pathway. DTNQ-Pro causes Caco-2 cell death by induction of apoptosis via inhibition of HSP70 accumulation and the intracellular redistribution of HSP27. These findings suggest the potential use of DTNQ-Pro in combination chemotherapy for colon cancer.

Heterocycles [h]-fused onto 4-oxoquinoline-3-carboxylic acid, Part VI [1]. Synthesis and X-ray structure of model indolo[3,2-b]- and [2,3-b]pyrido[2,3-f]quinoxaline-3-carboxylic esters

Cyclocondensation reaction of ethyl 7,8-diamino-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate with 1-methylisatin produced a separable mixture of the corresponding indolo[3,2-b]- and [2,3-b]pyrido[2,3-f]quinoxaline-3-carboxylates, of which the latter isomer predominates. On the other hand, interaction with 1H-isatin or 5-chloroisatin gave the respective indolo[2,3-b]pyrido[2,3-f]quinoxaline-3-carboxylates as the sole regiospecific products. The structures of these new pentacyclic derivatives are based on microanalytical, spectral (IR, MS, and NMR) and X-ray crystal structure data.