Improvement of Metabolic and Histological Changes of Adiposity in Rats by Synthetic Oleoyl Chalcones.

We previously reported that synthetic oleoyl chalcones had a favorable effect to alleviate metabolic consequences of obesity in male SD rats. In this work, we prepared and characterized by spectroscopic tools, a set of six oleoyl chalcones (5a-c, 10 and 11a,b). The comparative effects of the previously prepared oleoyl chalcones and their new synthetic analogs on metabolic and histological changes in obese male SD rats were studied. It was found that the oleoyl chalcones IIIa and IV were the best in improving many metabolic parameters, e. g., FBG, FI, ISI, TG, and total cholesterol. They cured systemic inflammation, through inhibition of the TNF-α and induction of adiponectin production. Moreover, chalcones IIIa and IV alleviated the oxidative stress accompanying obesity through the induction of the antioxidant enzymes GPX, SOD and CAT besides, GSH. Interestingly, chalcones IIIa and IV exerted hepatoprotective potency and ameliorated the manifestations of NAFLD via inhibition of apoptosis and induction of autophagy of hepatic cells. In conclusion, the oleoyl chalcones IIIa and IV were the most effective candidates among the series of synthetic chalcones in correcting body weight and the consequent metabolic and histological changes in adiposity.

Influence of nanoparticles on freezing inside container equipped with fins.

With loading of different shapes of nanoparticles, the solidification speed can be changed which was scrutinized in current work. Although the nanoparticles dispersion can decline the heat capacity, the conduction mode can be improved with such technique and changing the styles of nano-powders can alter the strength of conduction. The velocity terms were neglected in freezing, thus, the main equations include two equations with unsteady form for scalars of solid fraction and temperature. Grid adaption with position of ice front has been considered in simulations utilizing FEM. The upper sinusoidal and inner rectangular walls maintain cold temperature and freezing starts from these regions. Adding nanomaterial can expedite the process around 15.75% (for m = 4.8) and 29.8% (for m = 8.6). Also, utilizing particles with shapes of blade form can augment the freezing rate around 16.69%. The efficacy of m on freezing process rises around 4% with elevate of concentration of nanoparticles.

Charge-transfer chemistry of two corticosteroids used adjunctively to treat COVID-19. Part II: The CT reaction of hydrocortisone and dexamethasone donors with TCNQ and fluoranil acceptors in five organic solvents.

Hydrocortisone (termed as D1) and dexamethasone (termed as D2) are corticosteroids currently used to treat COVID-19. COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exploring additional chemical properties of drugs used in the treatment protocols for COVID-19 could help scientists alike improve these treatment protocols and potentially even the vaccines (i.e., Janssen, Moderna, AstraZeneca, Pfizer-BioNTech). In this work, the charge-transfer (CT) properties of these two corticosteroids (D1 and D2) with two universal acceptors: 7,8,8-tetracyanoquinodimethane (termed as TCNQ) and fluoranil (termed as TFQ) in five different solvents were investigated. The examined solvents were MeOH, EtOH, MeCN, CH2Cl2, and CHCl3. The CT interactions formed stable corticosteroid CT complexes in all examined solvents. Several spectroscopic parameters were derived, and the oscillator strength (f) and transition dipole moment (µe.g. ) values revealed that the interaction between the investigated corticosteroids with TCNQ acceptor is much stronger than their interaction with TFQ acceptor. The CT interactions were proposed to process via n â†’ π* transition.

Charge-transfer chemistry of two corticosteroids used adjunctively to treat COVID-19. Part I: Complexation of hydrocortisone and dexamethasone donors with DDQ acceptor in five organic solvents.

COVID-19 is the disease caused by a novel coronavirus (CoV) named the severe acute respiratory syndrome coronavirus 2 (termed SARS coronavirus 2 or SARS-CoV-2). Since the first case reported in December 2019, infections caused by this novel virus have led to a continuous global pandemic that has placed an unprecedented burden on health, economic, and social systems worldwide. In response, multiple therapeutic options have been developed to stop this pandemic. One of these options is based on traditional corticosteroids, however, chemical modifications to enhance their efficacy remain largely unexplored. Obtaining additional insight into the chemical and physical properties of pharmacologically effective drugs used to combat COVID-19 will help physicians and researchers alike to improve current treatments and vaccines (i.e., Pfizer-BioNTech, AstraZeneca, Moderna, Janssen). Herein, we examined the charge-transfer properties of two corticosteroids used as adjunctive therapies in the treatment of COVID-19, hydrocortisone and dexamethasone, as donors with 2,3-dichloro-5,6-dicyano-p-benzoquinone as an acceptor in various solvents. We found that the examined donors reacted strongly with the acceptor in CH2Cl2 and CHCl3 solvents to create stable compounds with novel clinical potential.

Vitamin D3 Prevents the Deleterious Effects of Testicular Torsion on Testis by Targeting miRNA-145 and ADAM17: In Silico and In Vivo Study.

Testicular torsion (TT) is the most common urological emergency in children and young adults that can lead to infertility in many cases. The ischemia-reperfusion (IR) injury due to TT has been implicated in the pathogenesis of testicular damage. The main pathological mechanisms of contralateral injury after ipsilateral TT are not fully understood. In the presented study, we investigated the molecular and microscopic basis of ipsilateral and contralateral testicular injury following ipsilateral testicular torsion detorsion (T/D) and explored the possible protective role of vitamin D3. The biochemical analysis indicated that IR injury following T/D significantly decreased the activity of testicular glutathione peroxidase (GPx) enzyme, level of serum testosterone, serum inhibin B, and expression of testicular miRNA145, while increased the activity of testicular myeloperoxidase (MPO) enzyme, level of testicular malondialdehyde (MDA), level of serum antisperm-antibody (AsAb), and expression of ADAM-17. The histological and semen analysis revealed that torsion of the testis caused damages on different tissues in testis. Interestingly, administration of vitamin D3 prior to the IR injury reversed the deterioration effect of IR injury on the testicular tissues as indicated by biochemical and histological analysis which revealed normal appearance of the seminiferous tubules with an apparent decrease in collagen fiber deposition in both ipsilateral and contralateral testes. Our results revealed that the protective effect of vitamin D3 treatment could be attributed to target miRNA145 and ADAM17 protein. To further investigate these findings, we performed a detailed molecular modelling study in order to explore the binding affinity of vitamin D3 toward ADAM17 protein. Our results revealed that vitamin D3 has the ability to bind to the active site of ADAM17 protein via a set of hydrophobic and hydrophilic interactions with high docking score. In conclusion, this study highlights the protective pharmacological application of vitamin D3 to ameliorate the damages of testicular T/D on the testicular tissues via targeting miRNA145 and ADAM17 protein.

Insights into the Bioprospecting of the Endophytic Fungi of the Medicinal Plant Palicourea rigida Kunth (Rubiaceae): Detailed Biological Activities.

A multitude of plants from the Brazilian savanna are known for their medicinal properties. Many plants contain endophytic fungi, which lead to the production of bioactive compounds by both the fungi and their hosts. This study investigated the bioprospecting of endophytic fungi recovered from the leaves of Palicourea rigida, a native medicinal plant of the Brazilian savanna. Four fungal taxa (Colletotrichum sp. SXS649, Pestalotiopsis sp. SXS650, the order Botryosphaeriales SXS651, and Diaporthe sp. SXS652) were recovered. The phenolic, flavonoid, extracellular degrading enzymes (amylase, cellulase, protease, and tannase) and antioxidant activity of these taxa were determined. Evaluation of the antimicrobial activity showed that the Botryosphaeriales SXS651 extract displays a minimum inhibitory concentration (MIC) of 23.20 mg mL-1 against Staphylococcus epidermidis and Pseudomonas aeruginosa, and the Diaporthe sp. SXS652 extract exhibited an MIC of 27.00 mg mL-1 against Escherichia coli. The Colletotrichum sp. SXS649 isolate inhibited tumors in potato discs by 69% at a concentration of 9.70 mg mL-1. All isolates had potential bioremediation criteria against soil contaminated with soybean oil, as proved by a high percentage of germination of Lactuca sativa and a reduction in phytotoxicity. Furthermore, the taxa under investigation demonstrated antagonistic action to phytopathogenic fungi, namely, Aspergillus niger, Inonotus rickii, Pestalotiopsis mangiferae, and Coniophora puteana, with an inhibition range between 34.2% and 76.9%. The preliminary toxicity assessment showed that all isolates possessed an LC50 of less than 100 mg mL-1 to the microcrustacean Artemia salina. These results indicate that the endophytic fungi of the Brazilian savanna are promising candidates for biotechnological and industrial applications and, in agricultural applications, for the biological control of phytopathogenic fungi.

Novel N-bridged pyrazole-1-carbothioamides with potential antiproliferative activity: design, synthesis, in vitro and in silico studies.

Thiazole-substituted pyrazole is an important structural feature of many bioactive compounds, including antiviral, antitubercular, analgesic and anticancer agents. Herein we describe an efficient and facile approach for the synthesis of two series of 36 novel N-bridged pyrazole-1-phenylthiazoles. The antiproliferative activity of a set of representative compounds was evaluated in vitro against different human cancer cell lines. Among the identified compounds, compound 18 showed potent anticancer activity against the examined cancer cell lines. The in silico molecular docking study revealed that compound 18 possesses high binding affinity toward both SK1 and CDK2. Overall, these results indicate that compound 18 is a promising lead anticancer compound which may be exploited for development of antiproliferative drugs.

Beneficial Features of Biochar and Arbuscular Mycorrhiza for Improving Spinach Plant Growth, Root Morphological Traits, Physiological Properties, and Soil Enzymatic Activities.

Biochar and arbuscular mycorrhizal fungi (AMF) can promote plant growth, improve soil properties, and maintain microbial activity. The effects of biochar and AMF on plant growth, root morphological traits, physiological properties, and soil enzymatic activities were studied in spinach (Spinacia oleracea L.). A pot experiment was conducted to evaluate the effect of biochar and AMF on the growth of spinach. Four treatments, a T1 control (soil without biochar), T2 biochar alone, T3 AMF alone, and T4 biochar and AMF together, were arranged in a randomized complete block design with five replications. The biochar alone had a positive effect on the growth of spinach, root morphological traits, physiological properties, and soil enzymatic activities. It significantly increased the plant growth parameters, such as the shoot length, leaf number, leaf length, leaf width, shoot fresh weight, and shoot dry weight. The root morphological traits, plant physiological attributes, and soil enzymatic activities were significantly enhanced with the biochar alone compared with the control. However, the combination of biochar and AMF had a greater impact on the increase in plant growth, root morphological traits, physiological properties, and soil enzymatic activities compared with the other treatments. The results suggested that the combined biochar and AMF led to the highest levels of spinach plant growth, microbial biomass, and soil enzymatic activity.

Environmental Streptococcus uberis Associated with Clinical Mastitis in Dairy Cows: Virulence Traits, Antimicrobial and Biocide Resistance, and Epidemiological Typing.

Mastitis remains a serious problem for dairy animals. The misappropriation of antimicrobial agents helps accelerate resistance, which poses a serious challenge in controlling environmental S. uberis infection. Here, we study the virulence attributes, antimicrobial and biocide resistance, and epidemiological typing of S. uberis recovered from bovine clinical mastitis in dairy farms of diverse hygienic interventions in Egypt. The overall S. uberis infection rate was 20.59%; all were multidrug-resistant (MDR). The sua gene was the most frequent virulence gene (42.02%), followed by pauA (40.57%), cfu (21.73%), skc (20.28%), and opp (11.59%). The erm(B) gene served as the predominant antimicrobial-resistant gene (75.36%), followed by fexA (52.63%) and tet(M), blaZ, and aac(6')aph(2″) genes (46.38% each). Of note, 79.71%, 78.26%, and 18.84% of S. uberis isolates harbored qacED1, qacC/D, and qacA/B genes, respectively. All analyzed isolates were S. uberis type I by their unique RFLP-PCR pattern. In conclusion, the sustained presence of pauA and sua genes throughout the investigated farms contributes to a better understanding of the bacterium's pathogenicity. Furthermore, MDR coupled with the existence of biocide resistance genes indicates the importance of S. uberis surveillance and the prudent use of antimicrobials in veterinary clinical medicine to avoid the dissemination of antimicrobial resistance.

Data on charge-transfer interaction between 1-methyl-3-trifluoromethyl-2-pyrazoline-5-one with PA, CLA, TFQ, DDQ and TCNQ π-acceptors.

This article is related to a research paper entitled "Exploring the charge-transfer chemistry of fluorine-containing pyrazolin-5-ones: The complexation of 1-methyl-3-trifluoromethyl-2-pyrazoline-5-one with five π-acceptors" [J. Mol. Liq. 331 (2021) 115814] [1]. Herein we present photographic data that showed the color change after mixing methanolic solutions of 1-methyl-3-trifluoromethyl-2-pyrazoline-5-one (donor) with each of the investigated π-acceptor [picric acid (PA), chloranilic acid (CLA), fluoranil (TFQ), DDQ, and TCNQ]. Stoichiometry data for the interaction of the donor with all acceptors determined in solution state by the spectrophotometric titration method and the Job's continuous variation method were presented. The data presented are useful for understand that the charge-transfer (CT) complexation between a donor and an acceptor, generally, is characterized by a strong color change, and to understand the stoichiometry between these molecules.

Charge-transfer interaction of aspartame and neotame with several π-acceptors: Stoichiometric data.

This data article is related to a research paper entitled ``Correlations between spectroscopic data for charge-transfer complexes of two artificial sweeteners, aspartame and neotame, generated with several π-acceptors'' [J. Mol. Liq. 333 (2021) 115904] [1]. Herein we present stoichiometric data of charge-transfer (CT) complexes generated from the interaction between aspartame and neotame with three π-acceptors in methanol solvent at room temperature. The investigated π-acceptors were picric acid (PA), chloranilic acid (CA), and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), where the methods used to determine the stoichiometry of the CT interaction were the spectrophotometric titration method and the Job's continuous variation method.

Charge-transfer chemistry of azithromycin, the antibiotic used worldwide to treat the coronavirus disease (COVID-19). Part III: A green protocol for facile synthesis of complexes with TCNQ, DDQ, and TFQ acceptors.

Investigating the chemical properties of molecules used to combat the COVID-19 pandemic is of vital and pressing importance. In continuation of works aimed to explore the charge-transfer chemistry of azithromycin, the antibiotic used worldwide to treat COVID-19, the disease resulting from infection with the novel SARS-CoV-2 virus, in this work, a highly efficient, simple, clean, and eco-friendly protocol was used for the facile synthesis of charge-transfer complexes (CTCs) containing azithromycin and three π-acceptors: 7,7,8,8-tetracyanoquinodimethane (TCNQ), 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), and tetrafluoro-1,4-benzoquinone (TFQ). This protocol involves grinding bulk azithromycin as the donor (D) with the investigated acceptors at a 1:1 M ratio at room temperature without any solvent. We found that this protocol is environmentally benign, avoids hazardous organic solvents, and generates the desired CTCs with excellent yield (92-95%) in a straightforward means.

Emergence of Colistin and Carbapenem Resistance in Extended-Spectrum ß-Lactamase Producing Klebsiella pneumoniae Isolated from Chickens and Humans in Egypt.

This study investigated the frequency of carbapenem and colistin resistance in ESBL-producing K. pneumoniae (ESBLK) isolates recovered from chickens and their environment, contact farm workers and hospitalized patients in Egypt. Further, the phenotypic and genotypic relationships between the community and hospital-acquired K. pneumoniae isolates in the same geographical area were investigated. From 272 total samples, 37 (13.6%) K. pneumoniae isolates were identified, of which 20 (54.1%) were hypervirulent. All isolates (100%) were multidrug-resistant (MDR) with multiple antibiotic resistance (MAR) indices ranging from 0.19 to 0.94. Colistin-resistant isolates (18.9%) displayed colistin MIC values >2 µg/mL, all harbored the mcr-1 gene. All isolates from patients (13/90, 14.4%), workers (5/22, 22.7%), chickens (9/100, 9%) and the environment (10/60, 16.7%) harbored a single or multiple ß-lactamase genes, blaSHV, blaTEM, blaCTX-M1 and blaOXA-1, often in combination with carbapenemase genes (blaVIM, blaNDM-1 or blaIMP; 45.9%), the mcr-1 gene (18.9%) or both (13.5%). Enterobacterial repetitive intergenic consensus (ERIC)-PCR genotyping revealed 24 distinct ERIC types (ETs) with a discrimination index of 0.961. Six ETs showed clusters of identical isolates from chicken and human sources. The increased frequency and genetic relatedness of ESBLK and carbapenemase-producing K. pneumoniae (CPK) from chickens and humans pose a public health threat that urge more prudent use of antimicrobials in chicken farms to avoid the propagation and expansion of both ESBLK and CPK from the chicken sources to humans.

Quercetin/Zinc complex and stem cells: A new drug therapy to ameliorate glycometabolic control and pulmonary dysfunction in diabetes mellitus: Structural characterization and genetic studies.

Medicinal uses and applications of metals and their complexes are of increasing clinical and commercial importance. The ligation behavior of quercetin (Q), which is a flavonoid, and its Zn (II) (Q/Zn) complex were studied and characterized based on elemental analysis, molar conductance, Fourier-transform infrared (FTIR) spectra, electronic spectra, proton nuclear magnetic resonance (1H-NMR), thermogravimetric analysis, and transmission electron microscopy (TEM). FTIR spectral data revealed that Q acts as a bidentate ligand (chelating ligand) through carbonyl C(4) = O oxygen and phenolic C(3)-OH oxygen in conjugation with Zn. Electronic, FTIR, and 1H-NMR spectral data revealed that the Q/Zn complex has a distorted octahedral geometry, with the following chemical formula: [Zn(Q)(NO3)(H2O)2].5H2O. Diabetes was induced by streptozotocin (STZ) injection. A total of 70 male albino rats were divided into seven groups: control, diabetic untreated group and diabetic groups treated with either MSCs and/or Q and/or Q/Zn or their combination. Serum insulin, glucose, C-peptide, glycosylated hemoglobin, lipid profile, and enzymatic and non-enzymatic antioxidant levels were determined. Pancreatic and lung histology and TEM for pancreatic tissues in addition to gene expression of both SOD and CAT in pulmonary tissues were evaluated. MSCs in combination with Q/Zn therapy exhibited potent protective effects against STZ induced hyperglycemia and suppressed oxidative stress, genotoxicity, glycometabolic disturbances, and structural alterations. Engrafted MSCs were found inside pancreatic tissue at the end of the experiment. In conclusion, Q/Zn with MSC therapy produced a synergistic effect against oxidative stress and genotoxicity and can be considered potential ameliorative therapy against diabetes with pulmonary dysfunction, which may benefit against COVID-19.

Charge-transfer chemistry of azithromycin, the antibiotic used worldwide to treat the coronavirus disease (COVID-19). Part II: Complexation with several π-acceptors (PA, CLA, CHL).

Finding a vaccine or cure for the coronavirus disease (COVID-19) responsible for the worldwide pandemic and its economic, medical, and psychological burdens is one of the most pressing issues presently facing the global community. One of the current treatment protocols involves the antibiotic azithromycin (AZM) alone or in combination with other compounds. Obtaining additional insight into the charge-transfer (CT) chemistry of this antibiotic could help researchers and clinicians to improve such treatment protocols. Toward this aim, we investigated the CT interactions between AZM and three π-acceptors: picric acid (PA), chloranilic acid (CLA), and chloranil (CHL) in MeOH solvent. AZM formed colored products at a 1:1 stoichiometry with the acceptors through intermolecular hydrogen bonding. An n â†’ π* interaction was also proposed for the AZM-CHL CT product. The synthesized CT products had markedly different morphologies from the free reactants, exhibiting a semi-crystalline structure composed of spherical particles with diameters ranging from 50 to 90 nm.

Charge-transfer chemistry of azithromycin, the antibiotic used worldwide to treat the coronavirus disease (COVID-19). Part I: Complexation with iodine in different solvents.

Around the world, the antibiotic azithromycin (AZM) is currently being used to treat the coronavirus disease (COVID-19) in conjunction with hydroxychloroquine or chloroquine. Investigating the chemical and physical properties of compounds used alone or in combination to combat the COVID-19 pandemic is of vital and pressing importance. The purpose of this study was to characterize the charge transfer (CT) complexation of AZM with iodine in four different solvents: CH2Cl2, CHCl3, CCl4, and C6H5Cl. AZM reacted with iodine at a 1:1 M ratio (AZM to I2) in the CHCl3 solvent and a 1:2 M ratio in the other three solvents, as evidenced by data obtained from an elemental analysis of the solid CT products and spectrophotometric titration and Job's continuous variation method for the soluble CT products. Data obtained from UV-visible and Raman spectroscopies indicated that AZM strongly interacted with iodine in the CH2Cl2, CCl4, and C6H5Cl solvents by a physically potent n→σ* interaction to produce a tri-iodide complex formulated as [AZM·I+]I3 -. XRD and TEM analyses revealed that, in all solvents, the AZM-I2 complex possessed an amorphous structure composed of spherical particles ranging from 80 to 110 nm that tended to aggregate into clusters. The findings described in the present study will hopefully contribute to optimizing the treatment protocols for COVID-19.

Synthesis of Some New Folic Acid-Based Heterocycles of Anticipated Biological Activity.

To date, no fused heterocycles have been formed on folic acid molecules; for this reason, and others, our target is to synthesize new derivatives of folic acid as isolated or fused systems. Folic acid 1 reacted with ethyl pyruvate, triethyl orthoformate, ethyl chloroformate, thioformic acid hydrazide, and aldehydes to give new derivatives of folic acid 2-6a,b. Moreover, It reacted with benzylidene malononitrile, acetylacetone, ninhydrin, ethyl acetoacetate, ethyl cyanoacetate, and ethyl chloroacetate to give the pteridine fused systems 10-15, respectively. Ethoxycarbonylamino derivate 5 reacted with some nucleophiles containing the NH2 group, such as aminoguanidinium hydrocarbonate, hydrazine hydrate, glycine, thioformic acid hydrazide, and sulfa drugs in different conditions to give the urea derivatives 16-20a,b. Compound 4 reacted with the same nucleophiles to give the methylidene amino derivatives 21-24a,b. The fused compound 10 reacted with thioglycolic acid carbon disulfide, malononitrile, and formamide to give the four cyclic fused systems 25-30, respectively. The biological activity of some synthesized showed moderate effect against bacteria, but no effect shown towards fungi.

Measurements and correlations in solution-state for charge transfer products caused from the 1:2 complexation of TCNE acceptor with several important drugs.

In our previous work, we highlighted the thermodynamic and spectroscopic characteristics of the 1:1 charge transfer (CT) complexation of TCNE acceptor with various medically important drugs. Continuing that work, we further examine drugs that react with the TCNE acceptor via a 1:2 interaction. The examined drugs are atenolol, quinidine, cimetidine, reserpine, and levofloxacin. We aimed through this study to: i) make the spectrophotometric and thermodynamic data of the examined drugs, both initially and when reacted via a 1:2 M ratio with the TCNE acceptor, available to use in the determination or detection of these drugs in pharmaceuticals and other environments; and ii) compare the mode of interactions and the spectrophotometric and thermodynamic properties between drugs that react via a 1:1 or 1:2 ratio with the TCNE acceptor. To achieve these aims, the five examined drugs were reacted with TCNE in acetonitrile (MeCN) solvent at room temperature. Several thermodynamic and spectroscopic data were experimentally estimated using the van't Hoff and the Benesi-Hildebrand equations and discussed.

Synthesis and Pharmacological Studies of Unprecedented Fused Pyridazino[3',4':5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine Derivatives.

A novel fused system with three or four fused rings­pyridazino[3',4':5,6][1,2,4]triazino[4,3-b][1,2,4,5]tetrazine and pyridazino[3',4':5,6][1,2,4]triazino[3,4-b]pyrimido[4,5-e][1,3,4]thiadiazine was obtained from the starting materials 4(6H)-amino-3-hydrazino-7-(2-thienyl)pyridazino[3,4-e][1,2,4]-triazine 2 and 9-amino-3-(2-thienyl)-2H,8H-pyridazino[3',4':5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine-8-carbonitrile 12. Each of the starting compounds was subjected to a number of cyclization reactions to obtain a series of new heterocyclic fused systems, 3⁻10 and 13⁻23, via bifunctional reagents. Some of the synthesized compounds were screened against three cell lines including HepG2, HCT-116 and MCF-7 to discover their anticancer activity. The synthesized compounds were characterized depending on their elemental analyses and spectral data.

Synthesis of Some Novel Fused Pyrimido[4″,5″:5',6']-[1,2,4]triazino[3',4':3,4] [1,2,4]triazino[5,6-b]indoles with Expected Anticancer Activity.

Our current goal is the synthesis of polyheterocyclic compounds starting from 3-amino-[1,2,4]triazino[5,6-b]indole 1 and studying their anticancer activity to determine whether increasing of the size of the molecules increases the anticancer activity or not. 1-Amino[1,2,4]triazino[3',4':3,4]-[1,2,4]triazino[5,6-b]indole-2-carbonitrile (4) was prepared by the diazotization of 3-amino[1,2,4]-triazino[5,6-b]indole 1 followed by coupling with malononitrile in basic medium then cyclization under reflux to get 4. Also, new fused pyrimido[4″,5″:5',6'][1,2,4]triazino-[3',4':3,4][1,2,4]triazino[5,6-b]indole derivative 6 was prepared and used to obtain polycyclic heterocyclic systems. Confirmation of the synthesized compounds' structures was carried out using elemental analyses and spectral data (IR, ¹H-NMR and 13C-NMR and mass spectra). The anticancer activity of some of the synthesized compounds was tested against HepG2, HCT-116 and MCF-7 cell lines. The anticancer screening results showed that some derivatives display good activity which was more potent than that of the reference drug used. Molecular docking was used to predict the binding between some of the synthesized compounds and the prostate cancer 2q7k hormone and breast cancer 3hb5 receptors.