ANTIMICROBIAL AND ANTIOXIDANT ACTIVITY OF UREA/ THIOUREA DERIVATIVES OF 5-METHYL-3-(UREDIOMETHYL)-HEXANOIC ACID

A series of urea/ thiourea derivatives of 5-methyl-3-(urediomethyl)-hexanoic acid has been successfully synthesized from the reaction of 3-aminomethyl-5-methylhexanoic acid and aryl isocyanate/ aryl isothiocyanates in presence of triethylamine base in tetrahydrofuran solvent at rt-40C by stirring the contents for 3h

SYNTHESIS AND BIO-ACTIVITY STUDIES OF UREA/ THIOUREA DERIVATIVES OF 4,4'-DIAMINO BIPHENYL METHANE

The title compounds urea/ thiourea derivatives of 4,4'-diamino biphenyl methane were synthesized from the reaction of 4,4'-methylenedianiline with some aryl isocyanates and aryl isothiocyanates in the presence of 1,4-dimethyl piperazine catalyst and obtained the products with 80-91% yields. The structures of all the newly synthesized urea/ thiourea derivatives were confirmed by spectral (IR, 1H, 13C NMR & MS) and analytical studies

Hunig's base catalyzed synthesis of new 1-(2,3-dihydro-1H-inden-1-yl)-3-aryl urea/thiourea derivatives as potent antioxidants and 2HCK enzyme growth inhibitors

A series of 1-(2,3-dihydro-1H-indan-1-yl)-3-aryl urea/thiourea derivatives (4a-j) have been synthesized from the reaction of 2,3-dihydro-1H-inden-1-amine (2) with various aryl isocyanates/isothiocyanates (3a-j) by using N,N-DIPEA base (Hunig's base) catalyst in THF at reflux conditions. All of them are structurally confirmed by spectral (IR, 1H & 13C NMR and MASS) and elemental analysis and screened for their in-vitro antioxidant activity against DPPH and NO free radicals and found that compounds 4b, 4i, 4h & 4g are potential antioxidants. The obtained in vitro results were compared with the molecular docking, ADMET, QSAR and bioactivity study results performed for them and identified that the recorded in silico binding affinities were observed in good correlation with the in vitro antioxidant results. The Molecular docking analysis had unveiled the strong hydrogen bonding interactions of synthesized ligands with ARG 160 residue of protein tyrosine kinase (2HCK) enzyme and plays an effective role in its inhibition. Toxicology studies have assessed the potential risks of 4a-j and inferred that all of them were in the limits of potential drugs. The conformational analysis of 4a-j inferred that the urea/thiourea spacer linking 2,3-dihydro-1H-inden-1-amino and substituted aryl units has facilitated all these molecules to effectively bind with ARG 160 amino acid residue present on the α-helix of the protein tyrosine kinase (2HCK) enzyme specifically on chain A of hemopoetic cell kinase. Collectively this study has established a relationship between the antioxidant potentiality and ligands binding with ARG 160 amino acid residue of chain A of 2HCK enzyme to inhibit its growth as well as proliferation of reactive oxygen species in vivo. © 2019 Elsevier Inc.One of the authors Dr. Avula Vijay Kumar Reddy is thankful to Ural Federal University, Yekaterinburg, Russian Federation for providing Postdoctoral Fellowship

Marker‐Assisted Backcrossing to Introgress Resistance to Fusarium Wilt Race 1 and Ascochyta Blight in C 214, an Elite Cultivar of Chickpea

Fusarium wilt (FW) and Ascochyta blight (AB) are two major constraints to chickpea (Cicer arietinum L.) production. Therefore, two parallel marker-assisted backcrossing (MABC) programs by targeting foc1 locus and two quantitative trait loci (QTL) regions, ABQTL-I and ABQTL-II, were undertaken to introgress resistance to FW and AB, respectively, in C 214, an elite cultivar of chickpea. In the case of FW, foreground selection (FGS) was conducted with six markers (TR19, TA194, TAA60, GA16, TA110, and TS82) linked to foc1 in the cross C 214 × WR 315 (FW-resistant). On the other hand, eight markers (TA194, TR58, TS82, GA16, SCY17, TA130, TA2, and GAA47) linked with ABQTL-I and ABQTL-II were used in the case of AB by deploying C 214 × ILC 3279 (AB-resistant) cross. Background selection (BGS) in both crosses was employed with evenly distributed 40 (C 214 × WR 315) to 43 (C 214 × ILC 3279) SSR markers in the chickpea genome to select plant(s) with higher recurrent parent genome (RPG) recovery. By using three backcrosses and three rounds of selfing, 22 BC3F4 lines were generated for C 214 × WR 315 cross and 14 MABC lines for C 214 × ILC 3279 cross. Phenotyping of these lines has identified three resistant lines (with 92.7–95.2% RPG) to race 1 of FW, and seven resistant lines (with 81.7–85.40% RPG) to AB that may be tested for yield and other agronomic traits under multilocation trials for possible release and cultivation

Marker-Assisted Backcrossing to Introgress Resistance to Fusarium Wilt Race 1 and Ascochyta Blight in C 214, an Elite Cultivar of Chickpea

Fusarium wilt (FW) and Ascochyta blight (AB) are two major constraints to chickpea (Cicer arietinum L.) production. Therefore, two parallel marker-assisted backcrossing (MABC) programs by targeting foc1 locus and two quantitative trait loci (QTL) regions, ABQTL-I and ABQTL-II, were undertaken to introgress resistance to FW and AB, respectively, in C 214, an elite cultivar of chickpea. In the case of FW, foreground selection (FGS) was conducted with six markers (TR19, TA194, TAA60, GA16, TA110, and TS82) linked to foc1 in the cross C 214 × WR 315 (FWresistant). On the other hand, eight markers (TA194, TR58, TS82, GA16, SCY17, TA130, TA2, and GAA47) linked with ABQTL-I and ABQTL-II were used in the case of AB by deploying C 214 × ILC 3279 (AB-resistant) cross. Background selection (BGS) in both crosses was employed with evenly distributed 40 (C 214 × WR 315) to 43 (C 214 × ILC 3279) SSR markers in the chickpea genome to select plant(s) with higher recurrent parent genome (RPG) recovery. By using three backcrosses and three rounds of selfing, 22 BC3F4 lines were generated for C 214 × WR 315 cross and 14 MABC lines for C 214 × ILC 3279 cross. Phenotyping of these lines has identified three resistant lines (with 92.7–95.2% RPG) to race 1 of FW, and seven resistant lines (with 81.7–85.40% RPG) to AB that may be tested for yield and other agronomic traits under multilocation trials for possible release and cultivation

Increased circulating ANG II and TNF-α represents important risk factors in obese Saudi adults with hypertension irrespective of diabetic status and BMI

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk

Integrated physical, genetic and genome map of chickpea (Cicer arietinum L.)

Physical map of chickpea was developed for the reference chickpea genotype (ICC 4958) using bacterial artificial chromosome (BAC) libraries targeting 71,094 clones (~12× coverage). High information content fingerprinting (HICF) of these clones gave high-quality fingerprinting data for 67,483 clones, and 1,174 contigs comprising 46,112 clones and 3,256 singletons were defined. In brief, 574 Mb genome size was assembled in 1,174 contigs with an average of 0.49 Mb per contig and 3,256 singletons represent 407 Mb genome. The physical map was linked with two genetic maps with the help of 245 BAC-end sequence (BES)-derived simple sequence repeat (SSR) markers. This allowed locating some of the BACs in the vicinity of some important quantitative trait loci (QTLs) for drought tolerance and reistance to Fusarium wilt and Ascochyta blight. In addition, fingerprinted contig (FPC) assembly was also integrated with the draft genome sequence of chickpea. As a result, ~965 BACs including 163 minimum tilling path (MTP) clones could be mapped on eight pseudo-molecules of chickpea forming 491 hypothetical contigs representing 54,013,992 bp (~54 Mb) of the draft genome. Comprehensive analysis of markers in abiotic and biotic stress tolerance QTL regions led to identification of 654, 306 and 23 genes in drought tolerance “QTL-hotspot” region, Ascochyta blight resistance QTL region and Fusarium wilt resistance QTL region, respectively. Integrated physical, genetic and genome map should provide a foundation for cloning and isolation of QTLs/genes for molecular dissection of traits as well as markers for molecular breeding for chickpea improvement