Sinteza, struktura i solvatohromizam potencijalno farmakološki aktivnih derivata sukcinimida

In order to investigate solvent effects and molecular structure on the activity of N-phenylsuccinimide, derivatives three series of corresponding compounds have been synthesized. The first series represents N-(3- and 4- substituted phenyl)-2-methylsuccinimides, with substituents: hydrogen, metoxy, methyl, hydroxy, chlor, brom, acetyl, iod, carboxy and nitro group. The second compound consists of N-(3- and 4- substituted phenyl)-2-phenylsuccinimides, in reference to his with different substituents in 3- and 4- position of phenyl nucleus. The substituents are: hydrogen, methyl, metoxy, chlor, brom, nitro, hydroxy and acetyl group. The third series consists of N-(3- and 4- substituted phenyl)-2,2-diphenylsuccinimide with different substituents in 3- and 4- position of phenyl nucleus. The substituents are: hydrogen, methyl, metoxy, nitro, hydroxy, cyano, fluor, chlor, brom, iod and acetyl group. All the succinimides have been synthesized according to procedure given in the literature or their modification. The purity of the obtained compounds have been confirmed by the determining melting points and recording the UV, FTIR, 1HNMR and 13CNMR spectra. Solvent effects on the activity of investigated succinimides have been interpret on the basis of UV absorption maximum in different solvents. Protic solvents having higher polarity cause hypsochromic effect. Contrary, aprotic solvents shifted absorption maximums to the higher wavelengths and batochromic effect occurs. The quantitative assessment of solvent effects on the absorption maximums of the investigated molecules was carried out by the means of linear solvatochromic energy relationship, using Kamlet-Taft equation...U okviru proučavanja uticaja strukture na antikonvulzivnu aktivnost sukcinimida u ovom radu su sintetisane tri različite serije novih potencijalno farmakološki aktivnih derivata sukcinimida. Osnovni cilj istraživanja je uspostavljanje novog modela za procenu farmakološke aktivnosti sukcinimida primenom linearne korelacije solvatohromnih energija na apsorpcione maksimume proučavanih molekula u različitim rastvaračima. Prvu seriju sintetisanih molekula čine N-(3- i 4- supstituisani fenil)-2-fenilsukcinimidi (A) sa različitim supstituentima u položajima tri i četiri fenilnog jezgra. Supstituenti su: vodonik, metil, metoksi, hlor, brom, nitro, hidroksi i acetil grupa. Drugu seriju jedinjenja predstavljaju N-(3- i 4- supstituisani fenil)-2,2-difenil-sukcinimidi (B), sa različitim supstituentima u položajima tri i četiri fenilnog jezgra. Supstituenti su: vodonik, metil, metoksi, nitro, hidroksi, cijano, fluor, hlor, brom, jod i acetil grupa. Treću grupu jedinjenja predstavljaju N-(3- i 4- supstituisani fenil)-2-metilsukcinimidi (C) sa različitim supstituentima u položajima tri i četiri fenilnog jezgra. Supstituenti su: vodonik, metoksi, metil, hidroksi, hlor, brom, acetil, jod, karboksi i nitro grupa. Sinteze gore pomenutih molekula su izvedene na osnovu postupaka navedenih u literaturi, odnosno njihovih neznatnih modifikacija. Karakterizacija i identifikacija sintetisanih jedinjenja izvršena je određivanjem temperature topljenja i snimanjem UV, FTIR, 1H NMR, 13C NMR spektara. UV apsorpcioni maksimumi navedenih molekula određeni su u 15 rastvarača različitih polarnosti, u opsegu talasnih dužina 200-400 nm. Koncentracije rastvora su iznosile 10-4 mol/dm3. Povećanje polarnosti protičnih rastvarača izaziva pomeranje apsorpcionih maksimuma ka manjim talasnim dužinama, odnosno javlja se hipsohromni efekat. Kod aprotičnih rastvarača javlja se suprotan efekat, odnosno dolazi do pomeranja apsorpcionih maksimuma ka većim talasnim dužinama i pojave batohromnog efekta. Kvantitativna procena efekta rastvarača na apsorpcione maksimume izvršena je metodom linearne korelacije solvatohromnih energija, odnosno korelacije UV apsorpcionih maksimuma Kamlet-Taftovom (Kamlet-Taft) jednačinom..

Synthesis, structure and solvatochromism of potentially pharmacologically active derivates of succinimides

У оквиру проучавања утицаја структуре на антиконвулзивну активност сукцинимида у овом раду су синтетисане три различите серије нових потенцијално фармаколошки активних деривата сукцинимида. Основни циљ истраживања је успостављање новог модела за процену фармаколошке активности сукцинимида применом линеарне корелације солватохромних енергија на апсорпционе максимуме проучаваних молекула у различитим растварачима. Прву серију синтетисаних молекула чине N-(3- и 4- супституисани фенил)-2-фенилсукцинимиди (А) са различитим супституентима у положајима три и четири фенилног језгра. Супституенти су: водоник, метил, метокси, хлор, бром, нитро, хидрокси и ацетил група. Другу серију једињења представљају N-(3- и 4- супституисани фенил)-2,2-дифенил-сукцинимиди (B), са различитим супституентима у положајима три и четири фенилног језгра. Супституенти су: водоник, метил, метокси, нитро, хидрокси, цијано, флуор, хлор, бром, јод и ацетил група. Трећу групу једињења представљају N-(3- и 4- супституисани фенил)-2-метилсукцинимиди (C) са различитим супституентима у положајима три и четири фенилног језгра. Супституенти су: водоник, метокси, метил, хидрокси, хлор, бром, ацетил, јод, карбокси и нитро група. Синтезе горе поменутих молекула су изведене на основу поступака наведених у литератури, односно њихових незнатних модификација. Карактеризација и идентификација синтетисаних једињења извршена је одређивањем температуре топљења и снимањем UV, FTIR, 1H NMR, 13C NMR спектара. UV апсорпциони максимуми наведених молекула одређени су у 15 растварача различитих поларности, у опсегу таласних дужина 200-400 nm. Концентрације раствора су износиле 10-4 mol/dm3. Повећање поларности протичних растварача изазива померање апсорпционих максимума ка мањим таласним дужинама, односно јавља се хипсохромни ефекат. Код апротичних растварача јавља се супротан ефекат, односно долази до померања апсорпционих максимума ка већим таласним дужинама и појаве батохромног ефекта. Квантитативна процена ефекта растварача на апсорпционе максимуме извршена је методом линеарне корелације солватохромних енергија, односно корелације UV апсорпционих максимума Камлет-Тафтовом (Kamlet-Taft) једначином...In order to investigate solvent effects and molecular structure on the activity of N-phenylsuccinimide, derivatives three series of corresponding compounds have been synthesized. The first series represents N-(3- and 4- substituted phenyl)-2-methylsuccinimides, with substituents: hydrogen, metoxy, methyl, hydroxy, chlor, brom, acetyl, iod, carboxy and nitro group. The second compound consists of N-(3- and 4- substituted phenyl)-2-phenylsuccinimides, in reference to his with different substituents in 3- and 4- position of phenyl nucleus. The substituents are: hydrogen, methyl, metoxy, chlor, brom, nitro, hydroxy and acetyl group. The third series consists of N-(3- and 4- substituted phenyl)-2,2-diphenylsuccinimide with different substituents in 3- and 4- position of phenyl nucleus. The substituents are: hydrogen, methyl, metoxy, nitro, hydroxy, cyano, fluor, chlor, brom, iod and acetyl group. All the succinimides have been synthesized according to procedure given in the literature or their modification. The purity of the obtained compounds have been confirmed by the determining melting points and recording the UV, FTIR, 1HNMR and 13CNMR spectra. Solvent effects on the activity of investigated succinimides have been interpret on the basis of UV absorption maximum in different solvents. Protic solvents having higher polarity cause hypsochromic effect. Contrary, aprotic solvents shifted absorption maximums to the higher wavelengths and batochromic effect occurs. The quantitative assessment of solvent effects on the absorption maximums of the investigated molecules was carried out by the means of linear solvatochromic energy relationship, using Kamlet-Taft equation..

Design and In Vitro Biological Evaluation of a Novel Organotin(IV) Complex with 1-(4-Carboxyphenyl)-3-ethyl-3-methylpyrrolidine-2,5-dione

A novel triphenyltin(IV) compound with 1-(4-carboxyphenyl)-3-ethyl-3-methylpyrrolidine-2,5-dione was synthesized and characterized by IR, NMR spectroscopy, mass spectrometry, and elemental analysis. In vitro anticancer activity of ligand precursor and synthesized organotin(IV) compound was determined against tumor cell lines: human adenocarcinoma (HeLa), human myelogenous leukemia (K562), and human breast cancer (MDA-MB-453), using microculture tetrazolium test (MTT) assay. The results indicate that complex exhibited very high antiproliferative activity against all tested cell lines with IC50 values in the range of 0.22 to 0.53 mu M. The highest activity organotin(IV) compound expressed against the HeLa cells (IC50=0.22 +/- 0.04 mu M). The ligand precursor did not show anticancer activity (IC50>200 mu M). Furthermore, fluorescence microscopy analysis of HeLa cells reveal that organotin(IV) complex induced apoptosis as a mode of cell death, which is consistent with the increase of cells in the sub-G1 phase

Procena antikancerogene aktivnosti novih organokalaj(IV) jedinjenja koja sadrže derivate 2-propanske kiseline

Two novel organotin(IV) compounds containing 2-propanoic acid derivatives were synthesized and characterized by standard spectroscopic methods. In vitro antiproliferative activity of these complexes was investigated versus four tumor cell lines: PC3 (prostate), HT-29 (colon), MCF-7 (breast) and HepG2 (hepatic) using MTT and CV assays. The results have shown that that synthesized complexes exhibit remarkable anticancer activity toward all tested cell lines with 54 to 113 fold higher activity than the reference compound cisplatin. The obtained promising results indicate the necessity for further in vitro/in vivo research with the aim to investigate the mechanism of action of these potencial antitumor agents.Dva nova organokalaj(IV) jedinjenja, koja sadrže derivate 2-propanske kiseline, sintetisana su i okarakterisana pomoću standardnih spektroskopskih metoda. In vitro antiproliferativna aktivnost ovih jedinjenja ispitana je prema četiri tumorske ćelijske linije: PC3 (prostata), HT-29 (debelo crevo), MCF-7 (dojka) i HepG2 (jetra) pomoću MTT and CV testova. Rezultati ispitivanja ukazuju da sintetisana jedinjenja ispoljavaju izvanrednu antikancerogenu aktivnost prema svim ispitanim ćelijskim linijama i njihova aktivnost je od 54 do 113 puta veća od aktivnosti referentne supstance, cisplatine. Dobijeni rezultati ukazuju na neophodnost daljih in vitro/in vivo istraživanja sa ciljem ispitivanja mehanizma delovanja ovih potencijalnih antitumorskih agenasa

Procena antikancerogene aktivnosti novih organokalaj(IV) jedinjenja koja sadrže derivate 2-propanske kiseline

Two novel organotin(IV) compounds containing 2-propanoic acid derivatives were synthesized and characterized by standard spectroscopic methods. In vitro antiproliferative activity of these complexes was investigated versus four tumor cell lines: PC3 (prostate), HT-29 (colon), MCF-7 (breast) and HepG2 (hepatic) using MTT and CV assays. The results have shown that that synthesized complexes exhibit remarkable anticancer activity toward all tested cell lines with 54 to 113 fold higher activity than the reference compound cisplatin. The obtained promising results indicate the necessity for further in vitro/in vivo research with the aim to investigate the mechanism of action of these potencial antitumor agents.Dva nova organokalaj(IV) jedinjenja, koja sadrže derivate 2-propanske kiseline, sintetisana su i okarakterisana pomoću standardnih spektroskopskih metoda. In vitro antiproliferativna aktivnost ovih jedinjenja ispitana je prema četiri tumorske ćelijske linije: PC3 (prostata), HT-29 (debelo crevo), MCF-7 (dojka) i HepG2 (jetra) pomoću MTT and CV testova. Rezultati ispitivanja ukazuju da sintetisana jedinjenja ispoljavaju izvanrednu antikancerogenu aktivnost prema svim ispitanim ćelijskim linijama i njihova aktivnost je od 54 do 113 puta veća od aktivnosti referentne supstance, cisplatine. Dobijeni rezultati ukazuju na neophodnost daljih in vitro/in vivo istraživanja sa ciljem ispitivanja mehanizma delovanja ovih potencijalnih antitumorskih agenasa

Sukcinimidi - dobijanje, svojstva i antikonvulzivna aktivnost

Succinimide is a cycle imide of succinic acid that is present in numerous biologically active compounds including anticonvulsants, antitremor, anti-Parkinson's agents. This paper describes different ways of synthesis of succinimide derivatives, their physical properties and reactivity. Also, the most widely used succinimide anticonvulsants and the analysis of structure-activity relationships of anticonvulsant drugs in terms of lipophilicity and hydrogen bonding are presented here.Sukcinimidi su ciklični imidi ćilibarne (sukcinske) kiseline, koji se primenjuju u medicini kao antikonvulzivi. Mogu se, takođe, koristiti u tretiranju drugih cerebralnih oboljenja, kao na primer tremora, Parkinsonove bolesti, itd. U ovom radu su prikazani postupci dobijanja sukcinimida, koji se upotrebljavaju u medicini, kao i njihova struktura i fizičke i hemijske osobine. Razmatran je uticaj strukture na antikonvulzivnu aktivnost različitih derivata sukcinimida sa aspekta lipofilnosti i mogućnosti uspostavljanja vodoničnih veza

Uticaj rastvarača na apsorpcione spektre prehrambenih azo boja

The solvent influence on absorption spectra of food azo dyes was examined by the method of Linear Solvation Energy Relationships (LSER). For this purpose, six azo dyes were used: tartrazine (E 102), ponceau 4R (E 124), azorubin (E 122), brilliant black (E 151), amaranth (E 123) and gelb orange S (E 110). Absorption spectra of dissolved azo dye have been recorded in the wavelength range of visible radiation, or from 380 to 760 nm, in eight solvent of different polarity. The choice of the solvent was limited due to the high polarity of the azo dye molecules themselves. The effect of solvent dipolarity/polarizability and solvent/solute hydrogen bonding interaction are analysed by means of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The linear correlation of the absorption maxima with parameters of Kamlet-Taft solvatochrome equation yielded satisfactory results.Uticaj polarnosti rastvarača na apsorpcione spektre prehrambenih azo boja ispitivan je metodom linearne korelacije energije solvatacije (LSER). U ovu svrhu korišćeno je šest prehrambenih azo boja i to: tartrazin (E 102), ponceau 4R (E 124), azorubin (E 122), brilijant crna (E 151), amarant (E 123) i gelb oranž S (E 110). Apsorpcioni spektri rastvorenih azo boja određeni su u talasnom opsegu vidljivog zračenja, odnosno u opsegu od 380 do 760 nm, u osam rastvarača različite polarnosti. Polarnost samih boja je uticala na izbor malog broja polarnih rastvarača. Spektre ispitivanih azo boja karakteriše jedan apsorpcioni maksimum. Efekat polarnosti rastvarača i efakat vodoničnog vezivanja rastvarač-rastvorena supstanca ispitivan je primenom KamletTaftove solvatohromne jednačine. Linearna korelacija apsorbcionih maksimuma sa parametrima Kamlet-Taftove solvatohromne jednačine dala je zadovoljavajuće rezultate

Spectroscopic and quantum chemical elucidation of newly synthesized 1-aryl-3-methyl-3-phenylpyrrolidine-2,5-diones as potential anticonvulsant agents

Novel succinimide derivatives were synthesized from 3-methyl-3-phenylsuccinic acid and substituted anilines under solvent-free conditions by using microwave irradiation. All obtained compounds were characterized by ultraviolet (UV), Fourier-transform infrared (FT-IR), H-1 and C-13 nuclear magnetic resonance (NMR) spectroscopy as well as by elemental analysis. The influence of the substituent electronic effects on spectroscopic data was analyzed by applying the Hammett equation. Moreover, a detailed interpretation and comparison of experimentally obtained and theoretically calculated FT-IR, UV and NMR spectra was performed. Density functional theory (DFT) calculated data of the investigated succinimides were obtained and analyzed in order to determine their structural, spectroscopic and electronic properties. Furthermore, ADMET factor profiling and in-silico prediction of potential biological activities of novel succinimide derivatives have been performed

Voltammetric and Quantum Investigation of Selected Succinimides

A series of succinimide derivatives were studied using the cyclic and square wave voltammetry. Density function theory was used in order to determinate which of the structural parameters influence the electrochemical activity. The quantum chemical calculations of the investigated succinimides were linked with the experimental electrochemical data and used to propose the oxidation mechanism. The most active among studied succinimides is 1,3-diphenylsuccinimide. The results obtained from the cyclic and square wave voltammetry and quantum chemical calculations indicate that the investigated compounds undergo oxidation by irreversible, diffusion controlled process including transfer of 1e(-) and 1 proton. The voltammetric and DFT results signify that the mechanism of electrochemical oxidation of all compounds involve the conversion of carbonyl-methyne-phenyl segment or methylene group in free radical. This conversion proceeds by the loss of one proton one electron process