Indole-3-piperazinyl derivatives: novel chemical class of 5-HT(6) receptor antagonists

N₁-Arylsulfonyl-3-piperazinyl indole derivatives were designed and identified as a novel class of 5-HT₆ receptors ligands. All the compounds have high affinity and antagonist activity towards 5-HT₆ receptor. The compound 7a (K_i = 3.4 nM, functional assay IC₅₀ = 310 nM) shows enhanced cognitive effect when tested in NORT and Morris water maze models. Synthesis, SAR and PK profile of these novel compounds constitute the subject matter of this Letter.     

Traditional preparation and uses of cassava in Nigeria

Various methods of cassava preparation are practised by different ethnic groups in Nigeria. These methods involve peeling cassava roots, soaking roots in streams, grating cassava, and pressing grated cassava. Other methods include heating sieved, grated cassava, boiling peeled cassava roots, and pounding boiled or dried cassava roots. The traditional, cassava-based products aregari, fufu, akpu, cassava flour, edible starch, and tapioca. Detoxification of fresh cassava roots is partly achieved through cell rupture during cutting and grating, soaking in running or standing water in earthen pots for 3–5 days, heating, drying, and boiling.     

Electronic and Defective Engineering of Electrospun CaMnO3 Nanotubes for Enhanced Oxygen Electrocatalysis in Rechargeable Zinc–Air Batteries

Rational design and massive production of bifunctional catalysts with superior oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activities are essential for developing metal–air batteries and fuel cells. Herein, controllable large‐scale synthesis of sulfur‐doped CaMnO₃ nanotubes is demonstrated via an electrospinning technique followed by calcination and sulfurization treatment. The sulfur doping can not only replace oxygen atoms to increase intrinsic electrical conductivity but also introduce abundant oxygen vacancies to provide enough catalytically active sites, which is further demonstrated by density functional theory calculation. The resulting sulfur‐modified CaMnO₃ (CMO/S) exhibits better electrocatalytic activity for ORR and OER in alkaline solution with higher stability performance than the pristine CMO. These results highlight the importance of sulfur treatment as a facile yet effective strategy to improve the ORR and OER catalytic activity of the pristine CaMnO₃. As a proof‐of‐concept, a rechargeable Zn–air battery using the bifunctional catalyst exhibits a small charge–discharge voltage polarization, and long cycling life. Furthermore, a solid‐state flexible and rechargeable Zn–air battery gives superior discharge–charge performance and remarkable stability. Therefore, the CMO/S nanotubes might be a promising replacement to the Pt‐based electrocatalysts for metal–air batteries and fuel cells.     

Indoleamines and calcium enhance somatic embryogenesis in <Emphasis Type="Italic">Coffea canephora</Emphasis> P ex Fr

Melatonin (MEL) and serotonin (SER) are important indoleamines that are involved in neural transmission in mammalian cells. They are also known to be present in various genera of plants. The role (s) of these indoleamines in plants are not well known. In this study, the effects of SER, MEL, calcium, and calcium ionophore (A23187), a calcium channel activator, on somatic embryogenesis in Coffea canephora have been investigated. Adding 100 μM of either SER or MEL to ½ strength Murashige and Skoog (MS) medium and 0.93 μM kinetin (KN) has resulted in enhanced induction of somatic embryogenesis, 85 ± 3 and 62 ± 6 embryos/callus, respectively. In the presence of either 5 mM calcium or 100 μM calcium ionophore A23187, number of somatic embryos/callus is also increased, with 56 ± 4 and 118 ± 10 somatic embryos/callus, respectively, compared to 25 ± 3 embryos/callus for control. The presence of 5 mM calcium chloride along with either 100 μM SER or 100 μM MEL, respectively, have also promoted somatic embryogenesis with induction of 105 ± 6 and 78 ± 2 somatic embryos/callus. While, addition of calcium ionophore A23187 along with either 100 μM SER or 100 μM MEL have produced 155 ± 12 or 135 ± 8 embryos/callus, respectively. In contrast, addition of such indoleamine inhibitors as 40 μM p-chlorophenylalanine (p-CPA), 20 μM fluoexitine hydrochloride (prozac), 1 mM verapamil hydrochloride (calcium channel blocker), and 1 mM ethylene glycol-bis (β-amino ethylether)-N, N, N′, N′-tetra acetic acid (EGTA) (a calcium chelator) individually, has inhibited induction of somatic embryos while reducing levels of endogenous pools of SER, MEL and indole-3-acetic acid (IAA) levels. Calcium imaging by laser scanning confocal microscopy (LSCM) has revealed high fluorescence intensity in callus treated with calcium and calcium ionophore A23187. Immunolocalization of SER in different tissues of C. canephora has revealed that it is localized in vascular tissues of stems, roots, and somatic embryos, as well as in endocarps (husks) of immature fruits.     

Comparative analysis of divergent and convergent gene pairs and their expression patterns in rice, Arabidopsis, and populus

Comparative analysis of the organization and expression patterns of divergent and convergent gene pairs in multiple plant genomes can identify patterns that are shared by more than one species or are unique to a particular species. Here, we study the coexpression and interspecies conservation of divergent and convergent gene pairs in three plant species: rice (Oryza sativa), Arabidopsis (Arabidopsis thaliana), and black cottonwood (Populus trichocarpa). Strongly correlated expression levels between divergent and convergent genes were found to be quite common in all three species, and the frequency of strong correlation appears to be independent of intergenic distance. Conservation of divergent or convergent arrangement among these species appears to be quite rare. However, conserved arrangement is significantly more frequent when the genes display strongly correlated expression levels or have one or more Gene Ontology (GO) classes in common. A correlation between intergenic distance in divergent and convergent gene pairs and shared GO classes was observed, in varying degrees, in rice and Populus but not in Arabidopsis. Furthermore, multiple GO classes were either overrepresented or underrepresented in Arabidopsis and Populus gene pairs, while only two GO classes were underrepresented in rice divergent gene pairs. Three cis-regulatory elements common to both Arabidopsis and rice were overrepresented in the intergenic regions of strongly correlated divergent gene pairs compared to those of noncorrelated pairs. Our results suggest that shared as well as unique mechanisms operate in shaping the organization and function of divergent and convergent gene pairs in different plant species.     

Synthesis and screening of (E)-1-(β-D-galactopyranosyl)-4-(aryl)but-3-ene-2-one against Mycobacterium tuberculosis

A series of galactose-derived aryl enones were synthesised and screened against Mycobacterium tuberculosis H₃₇Rv. Preliminary results were promising with MIC values in the range 1.56-12.5 μg/mL.     

Discovery of 3-hydroxy-4-cyano-isoquinolines as novel, potent, and selective inhibitors of human 11β-hydroxydehydrogenase 1 (11β-HSD1)

Derived from the HTS hit 1, a series of hydroxyisoquinolines was discovered as potent and selective 11β-HSD1 inhibitors with good cross species activity. Optimization of substituents at the 1 and 4 positions of the isoquinoline group in addition to the core modifications, with a special focus on enhancing metabolic stability and aqueous solubility, resulted in the identification of several compounds as potent advanced leads.     

Insights into the structure–function relationship of brown plant hopper resistance protein,Bph14 of rice plant: a computational structural biology approach

Brown plant hopper (BPH) is one of the major destructive insect pests of rice, causing severe yield loss. Thirty-two BPH resistance genes have been identified in cultivated and wild species of rice Although, molecular mechanism of rice plant resistance against BPH studied through map-based cloning, due to non-existence of NMR/crystal structures of Bph14 protein, recognition of leucine-rich repeat (LRR) domain and its interaction with different ligands are poorly understood. Thus, in the present study, in silico approach was adopted to predict three-dimensional structure of LRR domain of Bph14 using comparative modelling approach followed by interaction study with jasmonic and salicylic acids. LRR domain along with LRR-jasmonic and salicylic acid complexes were subjected to dynamic simulation using GROMACS, individually, for energy minimisation and refinement of the structure. Final binding energy of jasmonic and salicylic acid with LRR domain was calculated using MM/PBSA. Free-energy landscape analysis revealed that overall stability of LRR domain of Bph14 is not much affected after forming complex with jasmonic and salicylic acid. MM/PBSA analysis revealed that binding affinities of LRR domain towards salicylic acid is higher as compared to jasmonic acid. Interaction study of LRR domain with salicylic acid and jasmonic acid reveals that THR987 of LRR form hydrogen bond with both complexes. Thus, THR987 plays active role in the Bph14 and phytochemical interaction for inducing resistance in rice plant against BPH. In future, Bph14 gene and phytochemicals could be used in BPH management and development of novel resistant varieties for increasing rice yield.