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In an attempt to develop potent anti-cancer agents, a new 1,3,4-substituted-thiadiazole derivatives (8b-g), starting from 4-substituted-thiazol-2-chloroacetamides (4b-g), were synthesized and evaluated for their cytotoxic effects on multiple human cancer cell lines, including the hepatocellular carcinoma (HEPG-2), human lung carcinoma (A549), human breast carcinoma (MCF-7) and pseudo-normal human embryonic liver (L02) cancer cell lines by an MTT assay. Among all synthesized compounds, compound 8d showed the potent anti-cancer activities with GI 50 values of 2.98, 2.85 and 2.53 μM against MCF-7, A549 and HepG-2 cell lines respectively as compared to standard drug Doxorubicin. Furthermore, molecular modelling studies have spotlighted the anchoring role of 1,3,4-substituted-thiadiazole moiety in bonding and hydrophobic interaction with the key amino acid residues. Therefore, these results can provide promising starting points for further development of best anti-cancer agents., (© 2024. The Author(s).)

Tuberculosis remains a global health threat, with increasing infection rates and mortality despite existing anti-TB drugs. The present work focuses on the research findings regarding the development and evaluation of thiadiazole-linked thiazole derivatives as potential anti-tuberculosis agents. We present the synthesis data and confirm the compound structures using spectroscopic techniques. The current study reports twelve thiazole-thiadiazole compounds (5 a-5 l) for their anti-tuberculosis and related bioactivities. This paper emphasizes compounds 5 g, 5 i, and 5 l, which exhibited promising MIC values, leading to further in silico and interaction analysis. Pharmacophore mapping data included in the present analysis identified tubercular ThyX as potential drug targets. The compounds were evaluated for anti-tubercular activity using standard methods, revealing significant MIC values, particularly compound 5 l, with the best MIC value of 7.1285 μg/ml. Compounds 5 g and 5 i also demonstrated moderate to good MIC values against M. tuberculosis (H37Ra). Structural inspection of the docked poses revealed interactions such as hydrogen bonds, halogen bonds, and interactions containing Pi electron cloud, shedding light on conserved interactions with residues like Arg 95, Cys 43, His 69, and Arg 87 from the tubercular ThyX enzyme., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Improved Samba Mahsuri (ISM) is an elite, high-yielding, bacterial blight resistant, fine-grained rice variety with low glycaemic index. It is highly sensitive to salt stress, particularly at seedling stage, which significantly reduces its yield potential in coastal areas. A salinity tolerant QTL, Saltol, associated with seedling stage tolerance was previously mapped on chromosome 1 (10.6-11.5 Mb) from the Indian landrace, Pokkali and is effective in different genetic backgrounds. The objective of this study was to enhance salinity tolerance of ISM by incorporating the Saltol QTL through marker-assisted backcross breeding using the breeding line, FL478 (Pokkali/IR29)., Results: Foreground selection was carried out at each generation using five Saltol-specific markers and three bacterial blight resistance genes, Xa21, xa13 and xa5. Background selection was conducted using 66 well distributed polymorphic SSR markers and at the BC 3 F 2 generation, a single plant with maximum recurrent parent genome recovery (95.3%) was identified and advanced to the BC 3 F 4 generation. Based on bacterial blight resistance, seedling stage salinity tolerance and resemblance to ISM, four advanced breeding lines were selected for testing in replicated experiments near Hyderabad, India. A promising near-isogenic line, DRR Dhan 58, was evaluated in multi-location trials-coastal salinity and it showed significant salinity tolerance, resistance to bacterial blight disease, high yield and excellent grain quality during the 2019 and 2020 trials. DRR Dhan 58 was 95.1% similar to ISM based on genotyping with the 90 K SNP chip. Whole genome resequencing analysis of Pokkali and FL478 which were salinity tolerant checks, ISM and DRR Dhan 58 showed a high degree of relatedness with respect to the candidate gene loci for Saltol and OsSKC1 (Shoot K + Concentration 1)., Conclusion: DRR Dhan 58, possessing Saltol and three bacterial blight resistance genes (Xa21, xa13 and xa5) in the genetic background of the Indian mega-variety of rice, Samba Mahsuri, was developed for potential cultivation in areas prone to seedling stage salinity, as well as areas with endemic bacterial blight disease. This entry had a 24% yield advantage over the recurrent parent ISM under coastal saline conditions in multi-location trials and was recently released for commercial cultivation in India., (© 2022. The Author(s).)

To combat the dreaded diseases in rice like bacterial blight (BB) and blast, host plant resistance has been advocated as the most suitable and sustainable method. Through the present study, we have successfully incorporated three major BB resistance genes, namely Xa21 , xa13 and xa5 into NLR3449, a high yielding, blast resistant, fine-grain type, popular rice variety through marker-assisted backcross breeding. Foreground selection was carried out using polymerase chain reaction based, gene-specific markers, namely pTA248 ( Xa21 ), xa13prom ( xa13 ) and xa5FM ( xa5 ) at each generation of backcrossing, while 127 polymorphic SSR markers spanning on 12 chromosomes were used for background selection and backcrossing was limited to two rounds. At BC 2 F 1 generation, a single plant (NLR-87-10) with 89.9% recovery, possessing all the three BB resistance genes was forwarded to BC 2 F 2 generation. A solitary BC 2 F 2 plant, namely NLR-87- 10-106 possessing all the three resistance genes and 96% genome recovery was identified and advanced through selfing until BC 2 F 4 generation by adopting pedigree-method of selection. Three best BC 2 F 4 lines, possessing high level of resistance against BB and blast, and equivalent or superior to NLR 34449 in terms of yield, grain quality and agro-morphological traits were identified and advanced for multilocation trials.

A doubled haploid (DH) population consisting of 125 DHLs derived from the popular rice hybrid, KRH-2 (IR58025A/KMR3R) was utilized for Quantitative Trait Loci (QTL) mapping to identify novel genomic regions associated with yield related traits. A genetic map was constructed with 126 polymorphic SSR and EST derived markers, which were distributed across rice genome. QTL analysis using inclusive composite interval mapping (ICIM) method identified a total of 24 major and minor effect QTLs. Among them, twelve major effect QTLs were identified for days to fifty percent flowering ( qDFF12-1 ), total grain yield/plant ( qYLD3-1 and qYLD6-1 ), test (1,000) grain weight ( qTGW6-1 and qTGW7-1 ), panicle weight ( qPW9-1 ), plant height ( qPH12-1 ), flag leaf length ( qFLL6-1 ), flag leaf width ( qFLW4-1 ), panicle length ( qPL3-1 and qPL6-1 ) and biomass ( qBM4-1 ), explaining 29.95-56.75% of the phenotypic variability with LOD scores range of 2.72-16.51. Chromosomal regions with gene clusters were identified on chromosome 3 for total grain yield/plant ( qYLD3-1 ) and panicle length ( qPL3-1 ) and on chromosome 6 for total grain yield/plant ( qYLD6-1 ), flag leaf length ( qFLL6-1 ) and panicle length ( qPL6-1 ). Majority of the QTLs identified were observed to be co-localized with the previously reported QTL regions. Five novel, major effect QTLs associated with panicle weight ( qPW9-1 ), plant height ( qPH12-1 ), flag leaf width ( qFLW4-1 ), panicle length ( qPL3-1 ) and biomass ( qBM4-1 ) and three novel minor effect QTLs for panicle weight ( qPW3-1 and qPW8-1 ) and fertile grains per panicle ( qFGP5-1 ) were identified. These QTLs can be used in breeding programs aimed to yield improvement after their validation in alternative populations., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-03045-7., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest in the publication., (© King Abdulaziz City for Science and Technology 2021.)

Heterocycles are the main structural motif of DNA and RNA and play a crucial role in various chemical reactions of metabolisms. Therefore, heterocyclic compounds show good physiological and pharmacological properties. Coumarin and pyrazole scaffolds are present in many commercial drug molecules and natural products. This review overviews the progress made in the synthesis and functionalization of the coumarin- pyrazole hybrid heterocycle. It also includes discussion on the possible reactive sites of heterocycles, functionalization, and mechanistic pathways to incorporate pyrazole pharmacophore unit in synthesis. Several synthesis and biological studies reveal that the combination of the coumarin-pyrazole moiety is a prominent structural motif to find lead compounds in drug discovery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

With an objective of mapping novel low soil P (Phosphorus) tolerance loci in the non-Pup1 type donor rice line, Wazuhophek, we screened a recombinant inbred line (RIL) mapping population consisting of 330 lines derived from the cross Wazuhophek x Improved Samba Mahsuri (which is highly sensitive to low soil P) in a plot with low soil P for tolerance associated traits. Molecular mapping with SSR markers revealed a total of 16 QTLs (seven major and nine minor QTLs), which are associated with low soil P tolerance related traits. Interestingly, a QTL hotspot, harbouring 10 out of 16 QTLs were identified on the short arm of chromosome 8 (flanked by the makers RM22554 and RM80005). Five major QTLs explaining phenotypic variance to an extent of 15.28%, 17.25%, 21.84%, 20.23%, and 18.50%, associated with the traits, plant height, shoot length, the number of productive tillers, panicle length and yield, respectively, were located in the hotspot. Two major QTLs located on chromosome 1, associated with the traits, total biomass and root to shoot ratio, explaining 15.44% and 15.44% phenotypic variance, respectively were also identified. Complex epistatic interactions were observed among the traits, grain yield per plant, days to 50% flowering, dry shoot weight, and P content of the seed. In-silico analysis of genomic regions flanking the major QTLs revealed the presence of key putative candidate genes, possibly associated with tolerance., Competing Interests: The authors have declared that no competing interests exist.

Improved-Samba-Mahsuri (ISM), a high-yielding, popular bacterial blight resistant (possessing Xa21, xa13, and xa5), fine-grain type, low glycemic index rice variety is highly sensitive to low soil phosphorus (P). We have deployed marker-assisted backcross breeding (MABB) approach for targeted transfer of Pup1, a major QTL associated with low soil P tolerance, using Swarna as a donor. A new co-dominant marker, K20-1-1, which is specific for Pup1 was designed and used for foreground selection along with functional markers specific for the bacterial blight resistance genes, Xa21, xa13, and xa5. A set of 66 polymorphic SSR marker were used for the background selection along with a pair of flanking markers for the recombination selection in backcross derived progenies and in BC 2 F 2 generation, 12 plants, which are homozygous for Pup1, all the three bacterial blight resistance genes and possessing agro-morphological traits equivalent to or better than ISM were selected and selfed to produce BC 2 F 3 s. They were evaluated in plots with low soil P and normal soil P at ICAR-IIRR, Hyderabad for their low soil P tolerance, and bacterial blight resistance and superior lines were advanced to BC 2 F 6 . One of the lines, when tested at multiple locations in India was found promising under both normal as well as low soil P conditions.

The study was undertaken to identify the quantitative trait loci (QTLs) governing yield and its related traits using a recombinant inbred line (RIL) population derived from the popular rice hybrid, KRH-2 (IR58025A/KMR3R). A genetic map spanning 294.2 cM was constructed with 126 simple sequence repeats (SSR) loci uniformly distributed across the rice genome. QTL analysis using phenotyping and genotyping information identified a total of 22 QTLs. Of these, five major effect QTLs were identified for the following traits: total grain yield/plant (qYLD3-1), panicle weight (qPW3-1), plant height (qPH12-1), flag leaf width (qFLW4-1) and panicle length (qPL3-1), explaining 20.23-22.76% of the phenotypic variance with LOD scores range of 6.5-10.59. Few genomic regions controlling several traits (QTL hotspot) were identified on chromosome 3 for total grain yield/plant (qYLD3-1) and panicle length (qPL3-1). Significant epistatic interactions were also observed for total grain yield per plant (YLD) and panicle length (PL). While most of these QTLs were observed to be co-localized with the previously reported QTL regions, a novel, major QTL associated with panicle length (qPL3-1) was also identified. SNP genotyping of selected high and low yielding RILs and their QTL mapping with 1,082 SNPs validated most of the QTLs identified through SSR genotyping. This facilitated the identification of novel major effect QTLs with much better resolution and precision. In-silico analysis of novel QTLs revealed the biological functions of the putative candidate gene (s) associated with selected traits. Most of the high-yielding RILs possessing the major yield related QTLs were identified to be complete restorers, indicating their possible utilization in development of superior rice hybrids.

We have recently introduced a non-chromatographic alternative for antibody (Ab) purification, one which does not require the use of Protein A. With this approach, polyclonal human or mouse immunoglobulins (IgG's) are captured almost quantitatively by Tween-20 micelles conjugated with a [chelator:divalent metal cation] complex. Target IgG structure remains native even following extraction from the surfactant aggregate. In the present work, we explore the effect of varying both components of the [metal:chelator] pair on the yield of purified Ab. Capture efficiency is observed to correlate with the formation of sufficiently large detergent aggregates, as determined by dynamic light scattering (DLS) and polyacrylamide gel electrophoresis (PAGE). This, in turn, depends on the rigidity and aromaticity of the chelator. Detergent aggregates are stable over a wide range of pH values (pH = 3-9). Under acidic conditions (3-3.8) they lead to good IgG recovery yields (70-78%) with purity similar to that obtained with Protein A chromatography while maintaining the monomeric state of the IgG's. Finally, the influence of the environment and the presence of various water-soluble chelators (e.g. EDTA, histidine, imidazole) on process efficiency, is described., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The dearth of high quality, three dimensional crystals of membrane proteins, suitable for X-ray diffraction analysis, constitutes a serious barrier to progress in structural biology. To address this challenge, we have developed a new crystallization medium that relies on the conjugation of surfactant micelles via base-pairing of complementary hydrophobic nucleosides. Base-pairs formed at the interface between micelles bring them into proximity with each other; and when the conjugated micelles contain a membrane protein, crystal nucleation centers can be stabilized, thereby promoting crystal growth. Accordingly, two hydrophobic nucleoside derivatives - deoxyguanosine (G) and deoxycytidine (C), each covalently bonded to a 10 carbon chain were synthesized and added to an aqueous solution containing octyl β-d-thioglucopyranoside micelles. These hydrophobic nucleosides induced the formation of oil-rich globules after 2days incubation at 19°C or after a few hours in the presence of ammonium sulfate; however, phase separation was inhibited by 100mM GMP. The presence of the membrane protein bacteriorhodopsin in the conjugated - micellar dispersion resulted in the growth within the colorless globules of a variety of purple crystals, the color indicating a functional protein. On this basis, we suggest that conjugation of micelles via base-pair complementarity may provide significant assistance to the structural determination of integral membrane proteins., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Scaffold hopping from the thiazolopyridine ureas led to thiazolopyridone ureas with potent antitubercular activity acting through inhibition of DNA GyrB ATPase activity. Structural diversity was introduced, by extension of substituents from the thiazolopyridone N-4 position, to access hydrophobic interactions in the ribose pocket of the ATP binding region of GyrB. Further optimization of hydrogen bond interactions with arginines in site-2 of GyrB active site pocket led to potent inhibition of the enzyme (IC50 2 nM) along with potent cellular activity (MIC=0.1 μM) against Mycobacterium tuberculosis (Mtb). Efficacy was demonstrated in an acute mouse model of tuberculosis on oral administration., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A novel, one-pot, and highly facile protocol has been devised for an easy access of a series of novel glycosyl carboxamides from aldehydes using diacetoxyiodobenzene in the presence of ionic liquid at ambient temperature.

A facile and high-yielding protocol for diverse benzotriazoles through intramolecular N-arylation of different o -chloro-1,2,3-benzotriazenes using CuI/Cs 2 CO 3 has been developed., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Leishmaniasis, a vector-borne parasitic disease resulting from infection of macrophages by obligate intracellular parasites of genus Leishmania, has been considered a major tropical disease by the World Health Organization. Generic pentavalent antimonials have been the mainstay for therapy in the endemic regions because of its efficacy and cost effectiveness. However, the growing incidence of resistance for the pentavalent antimony complex in endemic and non-endemic regions has seriously hampered their use in these regions. The second line drugs such as amphotericin B, paromomycin and miltefosine are the other alternatives, but they merely fulfill the desired requirements of a safe drug. The recent researches focused on plants have shown a wise way to get a true and potentially rich source of drug candidates against leishmaniasis, where alkaloids have been found more effective. The present review initially highlights the current status of leishmaniasis, synergy of the disease with HIV, therapeutic options available and in later sections summarizes all alkaloids, which have shown significant antileishmanial activities.

Glycans cover the surface of all mammalian cells. Several toxins and pathogens use these glycans to bind and infect the cell. Using a versatile modular synthetic strategy, we have developed biotinylated bi- and tetraantennary glycoconjugates to capture and detect E. coli and compared the capturing ability of these molecules to commercial polyclonal antibodies. Magnetic beads were coated with biotinylated glycoconjugate or antibody, and these beads were used to capture, isolate, and quantify bacterial recovery by using a luminescence assay. The glycoconjugate-coated magnetic beads outperformed antibody-coated magnetic beads in sensitivity and selectivity when compared under identical experimental conditions. Glycoconjugates could capture Escherichia coli from stagnant water, and the ability of a panel of glycoconjugates to capture a selection of pathogenic bacteria was also evaluated. To the best of our knowledge, this study represents the first comprehensive study that compares synthetic glycoconjugates and antibodies for E. coli detection. The glycoconjugates are also very stable and inexpensive. The results presented here are expected to lead to an increased interest in developing glycoconjugate-based high affinity reagents for diagnostics.

We report the modular synthesis of robust, biotinylated biantennary sialylglycoconjugates and their ability to differentiate between two type A influenza strains. This is the first demonstration of glycoconjugate-based discriminatory capture and detection of two strains of intact influenza virus, in the presence of the innate enzymatic activity of viral neuraminidases. We also demonstrate a "carboassay" using glycoconjugates as capture and reporter elements, which therefore, does not require antibodies. The capture of intact influenza viruses is of potential benefit for clinical diagnostics.

The design, synthesis, and initial inhibitory studies of di- and tetravalent glycoconjugates that target the heavy chain of botulinum neurotoxin A are reported.