Synthesis, Crystal Structure, and Biological Evaluation of Novel 5-Hydroxymethylpyrimidines

Pyrimidine displays a wide array of bioactivities, and thence, it is still considered a potent unit of new drug research. Its derivative, 5-hydroxymethylpyrimidine, can be found as a scaffold of nontypical nitrogen bases in DNA and as a core of some natural bioactive compounds. In this study, we obtained a series of 5-hydroxymethylpyrimidines that vary in the 4-position by the reduction of proper esters. All compounds were characterized by spectroscopic analysis, and single-crystal X-ray diffraction was performed for some of them. Biological investigations estimated cytotoxic properties against normal (RPTEC) and cancer (HeLa, HepaRG, Caco-2, AGS, A172) cell lines. It was found that the derivatives with an aliphatic amino group at the 4-position are generally less toxic to normal cells than those with a benzylsulfanyl group. Moreover, compounds with bulky constituents exhibit better anticancer properties, though at a moderate level. The specific compounds were chosen due to their most promising IC50 concentration for in silico study. Furthermore, antimicrobial activity tests were performed against six strains of bacteria and one fungus. They demonstrated that only derivatives with at least three carbon chain amino groups at the 4-position have weak antibacterial properties, and only the derivative with 4-benzylsulfanyl constituent exhibits any antifungal action.

New record of species Monascus purpureus in Iraq

This study was conducted in the Laboratory of Fungus in the Department of Biology / College of Science / University of Qadisiyah to isolate and diagnose some insulation from fungi isolated from imported dried fruits (raisins) in Qadisiyah province, Iraq. The isolations were diagnosed both morphologically and microscopically using the classification keys and to confirm the appearance and microscopic diagnosis diagnosed using polymerase chain reaction(PCR), And determine the sequence of nitrogen bases (Nucleotide sequence(of compound DNA products using ITS1 and ITS4. The results of the nucleotide sequence analysis of DNA (PCR product) compounding innate isolation and using BLAST to compare with data available at the U.S. National Center for Biotechnology Information (NCBI) have shown that this isolation belongs to the type Monascus purpureus. By comparing the sequence of nitrogen bases of isolated M. purpureus fungus in this study, it was found that there was a 100% similarity to many of the M. purpureus fungus isolates previously registered at the National Center for Biotechnology Information (NCBI), including those diagnosed in China (MT361825, MK359689, MW581230) and Japan (AB477248).

The Mode of SN38 Derivatives Interacting with Nicked DNA Mimics Biological Targeting of Topo I Poisons

The compounds 7-ethyl-9-(N-methylamino)methyl-10-hydroxycamptothecin (2) and 7-ethyl-9-(N-morpholino)methyl-10-hydroxycamptothecin (3) are potential topoisomerase I poisons. Moreover, they were shown to have favorable anti-neoplastic effects on several tumor cell lines. Due to these properties, the compounds are being considered for advancement to the preclinical development stage. To gain better insights into the molecular mechanism with the biological target, here, we conducted an investigation into their interactions with model nicked DNA (1) using different techniques. In this work, we observed the complexity of the mechanism of action of the compounds 2 and 3, in addition to their decomposition products: compound 4 and SN38. Using DOSY experiments, evidence of the formation of strongly bonded molecular complexes of SN38 derivatives with DNA duplexes was provided. The molecular modeling based on cross-peaks from the NOESY spectrum also allowed us to assign the geometry of a molecular complex of DNA with compound 2. Confirmation of the alkylation reaction of both compounds was obtained using MALDI–MS. Additionally, in the case of 3, alkylation was confirmed in the recording of cross-peaks in the 1H/13C HSQC spectrum of 13C-enriched compound 3. In this work, we showed that the studied compounds—parent compounds 2 and 3, and their potential metabolite 4 and SN38—interact inside the nick of 1, either forming the molecular complex or alkylating the DNA nitrogen bases. In order to confirm the influence of the studied compounds on the topoisomerase I relaxation activity of supercoiled DNA, the test was performed based upon the measurement of the fluorescence of DNA stain which can differentiate between supercoiled and relaxed DNA. The presented results confirmed that studied SN38 derivatives effectively block DNA relaxation mediated by Topo I, which means that they stop the machinery of Topo I activity.

Higher Dimensions in the Theory of Heredity

On the basis Mendel's experiments, a mathematical model is constructed that describes the results of these experiments in a wide range of parameters. There is shown that in the mathematical model of Mendel's experiments, based on real patterns of plant development, there are equilibrium positions between the dominant and recessive forms. This equilibrium position is stable and located in the multidimensional space of system phenotypes. This newly discovered behavior of the dominant and recessive forms in the vicinity of the equilibrium position (true) differs significantly from the logistic equilibrium position in the Hardy-Weinberg principle, built without taking into account the real patterns in the plant population. The geometry of the neighborhood of the compound of two nucleic acid helices with nitrogen bases was investigated. It is proved that this neighborhood is a cross-polytope of dimension 13 (polytope of hereditary information), in the coordinate planes of which there are complementary hydrogen bonds of nitrogenous bases.

Phylogenetic analysis of kinetoplast DNA: kDNA of Leishmania tropica in Thi-Qar province, Iraq

IntroductionCutaneous leishmaniasis (CL) is one of wobbling endemic disease in Iraq, that cause intracellular obligate protistan parasite returned to the genus Leishmania. This study is aimed to identify epidemiology of CL, detect the prevalence of Leishmania tropica and find the phylogenetic relationship.MethodologyThe current study was conducted in the main hospitals of Thi-Qar province-south of Iraq for period from November 2018 to October 2019. Nested-PCR was used to amplify kinetoplast minicircle fragments DNA.ResultsIt was recorded 247 clinical cases with CL, the infections of males were higher than females, while infection rate appeared gradual reduction with age progress. Furthermore, the most CL infections were as single lesions and occurred in December. The infections of upper limbs were high when compared with other body regions. The molecular diagnosis showed L. tropica was more frequently. DNA sequences of kDNA gene of L. tropica showed confirmative genetic detection of local isolates using NCBI-Blast data and phylogenetic tree analysis after comparison with global recorded isolates. The local L. tropica isolates showed genetically closed related to NCBI-Blast L. tropica with accession number AB678350.1. Generally, the analysis of kDNA nitrogen bases sequences showed that all of samples were consistent with those recorded at the NCBI.ConclusionThe kDNA minicircle sequences analysis results showed mismatching of the local isolates decrease whenever approached from the Iranian border. In addition, genetic heterogeneity diagnosis is important for detection of therapy, control and epidemiological studies.

Novel fluorescence quenching triad based on molybdenum(V) tetra-p-tolylporphyrin and substituted fullero[60]pyrrolidine

With the aim of designing new photoactive donor–acceptor dyads, self-assembly in the (ethoxy)(oxo)(5,10,15,20-(4-methylphenyl)porphinato)molybdenum(V) (O=Mo(OEt)TTP)–2[Formula: see text]-(pyridin-4-yl)-5[Formula: see text]-(pyridin-2-yl)-1[Formula: see text]-(pyridin-2-yl-methyl)pyrrolidino[60]fullerene (Py3F)-toluene systems was quantitatively studied using spectral methods (UV-vis, IR, 1H NMR, mass spectrometry), chemical thermodynamics, and chemical kinetics. Interaction between O=Mo(OEt)TTP and pyridine (Py) proceeding as step equilibriums was preliminarily studied to model the processes above. The novel donor–acceptor triad based on O=Mo(OEt)TTP and Py3F is represented with both quantitative description of its formation and conformation of the chemical structure. Prospects for the study of the triad as a photosynthetic antenna imitator and an active layer in organic solar cells are substantiated by a fluorescence method. Along with this, it has been demonstrated that O=Mo(OEt)TTP is a good candidate for use as an optical and fluorescent chemosensor of volatile organic compounds and nitrogen bases — the building blocks of pharmaceuticals, food components and environmental pollutants.