Synthesis and characterization of Mannich bases of lawsone and their anticancer activity

Abstract

Natural and synthetic naphthoquinones are known for a large number of biological activities. Lawsone (2-hydroxy-1, 4-naphthoquinone) is a simplest naturally occurring compound obtained from dried henna (Lawsonia inermis) leaves. In literature, some lawsone derivatives have been reported to exhibit anticancer activity. Hence, a clean and facile one-pot protocol was developed for the synthesis of new aminonaphthoquinones derived from lawsone by three-component Mannich reaction, at room temperature for potential anti-cancer application. Herein we present a small library of Mannich bases with different amines and aromatic aldehydes with moderate to high yield. Synthesized compounds were characterized using various spectroscopic techniques. The anticancer activity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay) along with nuclear morphology assessment (4′,6-diamidino-2-phenylindole or DAPI staining), apoptosis assessment (acridine orange/ ethidium bromide staining), hemolysis and DNA ladder assay evaluated on human liver carcinoma cell line HepG2 are presented.     

Radioiodination and biodistribution of isolated lawsone compound from Lawsonia inermis (henna) leaves extract

Lawsonia inermis (henna) is one of the most effective medicinal plants and it has been using for treatment of wounds and burns for centuries. The using of Henna leaves is very popular for cosmetic as well as medicine in many countries. Henna leaves contain lots of different compounds and lawsone (LW) is the main one. In current study, extraction with bidistillated water of henna leaves was performed and LW was isolated by using high performance liquid chromatography system. Chemical structure of LW was evaluated by nuclear magnetic resonance method. LW was radiolabeled with iodine-131 (¹³¹I) radionuclide which is well known for nuclear imaging and therapy in nuclear medicine by utilizing iodogen method. The yield of radiolabeling of LW (¹³¹I-LW) was calculated as 92.70 ± 4.312 % (n = 10) by thin layer radio chromatography. Its in vivo biological activity was investigated by biodistribution studies which were performed by using healthy female and male Balb/C mice. According to results of biodistribution, uptake of ¹³¹I labeled LW compound in uterus, breast and ovary for female mice and prostate in male mice was higher than other organs in the body.     

Concise Synthesis and Pharmacological Applications of New α‐Lapachone Analogues

Synthesis of novel 1,4‐naphthoquinones structurally related to α‐lapachone skeleton and its annulated compounds were synthesized from lawsone (2‐hydroxynaphthalene‐1,4‐dione). Pharmacological studies provided indication of biological activities, including effects against hepatocellular carcinoma (HePG‐7) and mammary gland breast cancer (MCF‐7). The molecular structures of the target molecules were examined.     

Electrochemical studies on lawsone and its determination in henna (Lawsonia inermis) extract using glassy carbon electrode

The electrochemical behaviour of lawsone at glassy carbon electrode (GCE) was investigated by using cyclic and differential pulse anodic stripping voltammetric (DPASV) techniques. Cyclic voltammetry was used to study the influence of pH on the peak current and peak potential. The Mcllavnie’s buffer of pH 3.0 was selected as a suitable analytical medium in which lawsone exhibited sensitive diffusion controlled redox peaks (vs. Ag/AgCl). The peak current varied linearly with lawsone concentration in the range between 0.60 and 1.40 μM with a detection limit of 6 nM. The applicability of the proposed method was illustrated by the determination of lawsone present in real samples. A mean recovery of lawsone in the leaf of Lawsonia inermis was 99.5% with a relative standard deviation of 1.15%.     

Enhanced Raman spectrum of lawsone on Ag surface: vibrational analyses, frequency shifts, and molecular geometry

The surface-enhanced Raman spectrum of lawsone, a well known natural dye, has been investigated. Activation with KNO(3) or Na(2)SO(4) solution was necessary to enhance the Raman signal, whereas addition of NaCl solution depletes the effects. In the enhanced Raman spectrum, the strong double-bond stretching bands are most distinctive and show large red shifts from those in the infrared and FT-Raman spectra. The observed strong double-bond stretching bands reflect lawsone coordinated perpendicular to the Ag surface. DFT computations have been carried out for the plausible configurations of lawsone coordinated to an adatom on the Ag surface. Lawsone coordinated to an Ag(+) adatom with H(+) released best reproduces the observed vibrational characteristics.     

Biochemical study for the effect of henna (Lawsonia inermis) on Escherichia coli

Leaf samples of Lawsonia inermis (Li) were examined for their antimicrobial potential. Broth extracts in different concentrations were prepared and bioassayed in vitro for the growth of Escherichia coli. The growth of E. coli pathogen was inhibited to various degrees by increasing the concentration of the herbal powder. In addition to the observed alterations which were detected electrophoretically in the protein pattern, were activities of the amylase enzyme and glycoprotein fractions. The protein pattern has one common band of Rf 0.47 and two characteristic bands of Rf 0.36 and Rf 0.42 for E. coli sample. The quantitative mutation was observed in the bacteria with different concentrations of L. inermis compared with the control. Some types of proteins in E. coli completely disappeared upon being S.I affected. The amylase pattern showed one common band with Rf 0.037 and two characteristic bands with Rf 0.18 and Rf 0.37 for E. coli sample. The obvious quantitative mutation observed in bacteria with different concentrations of L. inermis compared with E. coli. The glycoprotein pattern recorded one common band at R₁ with Rf 0.94 for E. coli sample and bacteria inoculated with different concentrations of L. inermis. These results confirmed the antibacterial activity of henna leaves and supported the traditional use of the plant in therapy of bacterial infections and disturbances that occurred at the biochemical level. The broth extract of the L. inermis leaves showed obvious antibacterial activity against E. coli.     

Thermal and spectral properties of alkali metal complexes of 2-hydroxy-1,4-naphthoquinone

Thermal and spectral studies of reactions between 2-hydroxy-1,4-naphthoquinone (lawsone) and sodium metal (Lw-1, Lw-1A, Lw-1B), CH₃COONa (Lw-2), NaOH (Lw-3), KOH (Lw-4), K₂CO₃ (Lw-5), Tris buffer (Lw-6), ammonia (Lw-7) are studied. Red solids of Lw-1 to Lw-7, Lw-1A, and Lw-1B were isolated and are characterized by elemental analysis, FT-IR, ¹H NMR and UV–Visible spectroscopy. FT-IR spectra of Lw-1A and Lw-1B show, ν _OH of adsorbed as well as coordinated water molecules between 3,600–3,100 cm^?1 and decrease in ν _C=O frequency of lawsone ligand. The benzenoid ring protons C(5)H, C(8)H, C(6)H and C(7)H in Lw-1A and Lw-1B show upfield shift in ¹H NMR spectra. Hypsochromic shift and bathochromic shift is observed to π–π* transition band (~329 nm) and charge transfer band (~455 nm), respectively in UV–Visible spectra of all compounds. Pyrolytic decomposition of all compounds is studied by nonisothermal TG studies in air. Step I in all compounds leads to loss of adsorbed water molecules. Decomposition of lawsone anion in all compounds occurs in two or more steps. Thermodynamically Lw-1 to Lw-7, Lw-1A and Lw-1B are different compounds and their decomposition mechanisms are varied. The respective metal oxide residue viz. (Na₂O or K₂O) obtained after complete decomposition of Lw-1 to Lw-5, Lw-1A, and Lw-1B, is analyzed by powder X-ray diffraction. The adsorbed as well as coordinated water molecules are revealed by DTA and DSC studies as endothermic peak at ~100 °C. Decomposition mechanisms for lawsone anion are proposed based on LC–MS, GC–MS, and TG studies. Thermal and spectral studies reveal the coordination of lawsone ligand in its naphthosemiquinone form with alkali metal ions.     

SPME-GC-MS analysis of commercial henna samples (Lawsonia inermis L.)

The aim of this work was to provide a characterisation of volatile constituents from different commercial batches of henna (Lawsonia inermis) leaves of different geographic origin. Headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography–mass spectrometry (GC–MS) was used for the purpose. A total of 72 components were identified by GC–MS in the headspace of different henna samples which proved to differ considerably from each other, because they were characterised by different classes of components, mainly aliphatic compounds (9.0–64.7%), terpenoids (5.8–45.5%) and aromatics (7.9–45.2%), with alkanes (0.9–18.5%), aldehydes (2.1–18.8%) and carboxylic acids (3.1–29.3%), monoterpenes (3.4–30.0%) and sesquiterpenes (0.8–23.7%) and phenyl propanoids (0.6–43.1%), being the most abundant, respectively. Major representatives of these groups were n-hexadecane (0.5–4.7%), (2E)-hexenal (0.5–11.7%) and acetic acid (2.8–24.5%), limonene (0.8–14.7%), carvol (3.8–7.1%), geranyl acetone (1.4–7.9%) and (E)-caryophyllene (3.3–8.4%), and (E)-anethole (0.6–35.0%), respectively. We assume that factors such as the manufacturing process, the storage conditions and the different geographic origin of the samples may contribute to such variability.     

Efficient syntheses of streptocarpone and (±)-α-dunnione

An efficient divergent synthesis of both streptocarpone and racemic α-dunnione from lawsone are described. A one-pot, formal [3+2] cyclization to form a furanonaphthoquinone directly provided a common intermediate.     

Reactivity of indanedioneketene dimer with amines

The highly reactive indanedioneketene 5, resulting from the thermal decomposition of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone (lawsone, 4), in the absence of nucleophiles dimerizes to the corresponding tetraoxo spiro oxetanone 6 in quantitative yield. This oxetanone exhibits an interesting reactivity toward amines.     

Thermal Studies of Metal-quinone Complexes Role of Aqua Coligations with Copper(II) in Coordination of 2-hydroxy-1,4-naphthoquinone

Copper(II) complexes of lawsone (2-hydroxy-1,4-naphthaquinone, Lw) with variety of aqua ligation viz. Cu-1, [Cu(Lw)₂(H₂O)]₂; Cu-2, [Cu(Lw)₂(H₂O)₂] and Cu-3, [Cu(Lw)₂(H₂O)₂]₂ have been synthesized. The role of water as counter ligand on coordination propensity of redox active lawsone in naphthoquinone/naphthosemiquinone (NQ/NSQ) forms is quantified by studies of pyrolytic reactions, using non-isothermal TG and DTA techniques, coupled with IR studies. Mixed (NQ) (NSQ) ligation in Cu-1 and Cu-3 required energy of activation, E_a ∼67 kJ mol⁻¹ of (NQ) and ∼41 kJ mol⁻¹ of (NSQ). Comparable energies of aqua ligand (∼43 kJ mol⁻¹) with NSQ ligand in Cu-1 and Cu-3, dictate charge distributions in lawsone coordinations. A large difference between E_a of aqua and p-NQ ligand indicates coordination of lawsone in its fully oxidised quinone form in Cu-2. From thermoanalytical studies schematic oxidative decomposition mechanisms are proposed for Cu-1 and Cu-3. From pyrolytic reactions enthalpies are estimated by DTA technique. This revised version was published online in August 2006 with corrections to the Cover Date.     

Claisen Rearrangement of Hydroxynaphthoquinones: Selectivity toward Naphthofuran or α‐Xiloidone Using Copper Salts and Iodine

α‐xiloidone is an interesting chromene that are structurally related to lapachones; in this work, we selectively synthesized α‐xiloidone from the reaction of lawsone 1 with 3,3‐chloro‐3‐methylbut‐1‐yne under copper/I₂ catalysis via propargyl Claisen rearrangement.     

Dyeing behaviour of gamma irradiated cotton fabric using Lawson dye extracted from henna leaves (Lawsonia inermis)

Dyeing behavior of gamma irradiated cotton fabric using Lawson dye extracted from henna leaves has been investigated. Cotton and dye powder are irradiated to different absorbed doses of 2, 4, 6, 8 and 10 kGy using Cs-137 gamma irradiator. The dyeing parameters such as dyeing time, electrolyte (salt) concentration and mordant concentrations using copper and iron as mordants are optimized. Dyeing is performed using un-irradiated and irradiated cotton with dye solutions and their color strength values are evaluated in CIE Lab system using Spectraflash –SF650. Methods suggested by International Standard Organization (ISO) have been employed to investigate the colourfastness properties such as colourfastness to light, washing and rubbing of irradiated dyed fabric. It is found that gamma ray treatment of cotton dyed with extracts of henna leaves has significantly improved the color strength as well as enhanced the rating of fastness properties.     

Adaptable Access for Naphthaquinone Annulation: Bioactivity and Molecular Modeling Evaluations

A series of nitrogenous compounds containing 1,4‐naphhoquinone moiety such as lawsone, benzo[g]quinolone‐5,10‐diones, benzo[g]quinazoline‐5,10‐diones, and benzo[b] naphthodiazepine‐6,11‐diones analogs was synthesized by reaction of Lawsone (1) with different reagents. The structures of produced compounds were confirmed by variable spectra analysis. The molecular structures of the obtained molecules were studied. The products exhibited potent antioxidant and antitumor activities.     

Studies on the interaction of Eu(III) with lawsone (2-hydroxy-1,4-naphthoquinone), lapachol (2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone), juglone (5-hydroxy-1,4-naphthoquinone) and plumbagin (2-methyl-5-hydroxy-1,4-naphthoquinone)

pH-metric studies show that one mole of Eu(III) interacts with three molecules of each of juglone, plumbagin, lawsone and lapachol in solution. The stability and thermodynamics of these systems (50% aqueous acetone, 0.1 M KNO₃ ionic strength) are discussed and explained.     

Application of cobalt phthalocyanine as a nanostructured catalyst in the synthesis of biological henna‐based compounds

The present investigation describes synthesis of a good range of henna‐based compounds in the presence of novel nano cobalt phthalocyanine like molten salt (tetra‐2,3‐pyridiniumporphyrazinato cobalt tribromomethanide) [Co (TPPABr)]CBr₃ as an efficient, recyclable and thermally stable heterogeneous catalyst.     

Advanced Routes in Synthesis and Reactions of Lawsone Molecules (2‐Hydroxynaphthalene‐1,4‐dione)

Lawsone (2‐hydroxynaphthalene‐1,4‐dione ) is a natural product which shows significant biological activity. Lawsone has been found as a component of many dyes as well as a constituent of medicinal herbal treatments. So, this review aimed to document the publications concerning the synthesis and chemical reactivity and reactions of lawsone reported by research groups.     

Cyclic voltammetry for a preliminary study of appropriate electro-synthesis reactions of naphthalene derivatives

Cyclic voltammetry on a glassy carbon electrode was used for studies of electro-oxidations of several naphthalene derivatives. The number of electrons participating in the primary reaction at the electrode is derived using the modified Randles-Ševčik equation applied to a series of experimental data of peak current intensity vs. the potential rate. The mechanism of electro-oxidation of two natural products, juglone and lawsone, is discussed with respect to hydrogen bond formation. Correspondence: Roman E. Sioda, Department of Analytical Chemistry and Electrochemistry, Institute of Chemistry, University of Podlasie, ul. 3 Maja 54, 08-110 Siedlce, Poland. An erratum to this article can be found online at http://dx.doi.org/.     

Studies on the reactivity of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone: reactions with indole derivatives and other C-nucleophiles

[reaction: see text] Thermal decomposition of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone (lawsone) in the presence of indole derivatives affords 3-acylated indoles existing in their enol forms, through a ring contraction and alpha,alpha'-dioxoketene formation reaction. The same reactants afford 3-(3-indolyl)-2-hydroxy-1,4-naphthoquinones in a copper-catalyzed reaction. Enamines, among other C-nucleophiles tested, give analogous results.     

RDF法对非晶态聚醚砜共聚物的近程有序结构研究

用径向分布函数(RDF)研究了聚醚砜共聚物(PES)在r=1.5 nm范围内的近程结构, 结果表明, 分子链间存在近程有序结构, 有序周期约为0.5 nm; 聚醚砜共聚物经退火处理后, 由g(r)图可以看出, 第一个峰变高、变窄; 由G(r)图可以看出, 分子链间第一个有序区内, 分子链间贡献大于链内贡献; 于200 ℃退火处理后有序畴尺寸(rs)略有增大, 原子平均位移(σ)变小, 使得分子链内原子间距分布更加均匀, 相邻分子链间距(rv)变小. 同时透射电镜(TEM)的形态结构分析表明, 经退火处理后, 其聚集态确实形成了某种局部有序的结构.