Synthesis, anti-tuberculosis activity, and 3D-QSAR study of ring-substituted-2/4-quinolinecarbaldehyde derivatives

We have previously identified ring-substituted quinolines as a new structural class of anti-tuberculosis agents. In our ongoing efforts at structural optimization of this class, four series of ring-substituted-2/4-quinolinecarbaldehyde derivatives were synthesized. All twenty-four compounds were synthesized using short and convenient one to two high yielding steps. The newly synthesized compounds were tested in vitro against drug-sensitive Mycobacterium tuberculosis H37Hv strain. Several derivatives were found to be promising inhibitors of M. tuberculosis. For example, derivatives 4a-c (Series 2), 7a-d (Series 3), and 8a-b (Series 4) displayed >90% inhibition at 6.25 microg/mL in the primary assay. The most active compounds, N-(2-fluorophenyl)-N'-quinolin-2-ylmethylene-hydrazine (4a), N-(2-adamantan-1-yl-quinolin-4-ylmethylene)-N'-(4-fluorophenyl)hydrazine (7c), and N-(2-cyclohexyl-quinolin-4-ylmethylene)-N'-(2-fluorophenyl)hydrazine (8a), exhibited 99% inhibition at the lowest tested concentration of 3.125 microg/mL against drug-sensitive M. tuberculosis H37Rv strain. The similarity index based on steric and electrostatic features of the molecules was used, in conjunction with principal component analysis and linear discriminant analysis, successively to classify the molecules based on their activity into two classes. This classification method gives us confidence in predicting the activity class of any new unsynthesized molecule belonging to these series.     

Isolation and characterization of a rough microsomal fraction from rat kidney that is enriched in lysosomal enzymes

1. A special population of rough microsomal material (microsomes) rich in lysosomal acid hydrolases was separated by isopycnic centrifugation as a discrete fraction (RM(2)) from the bulk of rough microsomal material in rat kidney because of its greater density. 2. The specific activities of five acid hydrolases in the RM(2) fraction were approximately one-half those of a purified lysosomal (L) fraction and 10- to 30-fold greater than those of an ordinary rough microsomal (RM(1)) fraction. 3. These special rough microsomes have a distinctive ultrastructure and electron-cytochemical properties. Their cisternal content resembles the matrix of lysosomes in that it is electron-dense, osmiophilic and plumbophilic and gives a positive reaction for acid phosphatase activity. 4. Polyacrylamide-gel electrophoresis of soluble proteins from the L fraction resolved nine anionic glycoproteins, most of which exhibit acid hydrolase activities (Goldstone & Koenig, 1970, 1973; Goldstone et al., 1971a). The most anionic glycoprotein is the acidic lipoglycoprotein of the lysosomal matrix (Goldstone et al., 1970). 5. Polyacrylamide-gel electrophoresis of soluble proteins from the RM(2) fraction resolved two cationic glycoproteins with acid hydrolase activities (Goldstone & Koenig, 1973) and an anionic glycoprotein with the same electrophoretic mobility as the lysosomal lipoglycoprotein, but without its lipid constituents or capacity to bind the basic fluorochrome Acridine Orange. These constituents are considered to be the precursors of the lysosomal glycoproteins.     

Karyotype studies in the genusNotopterus (Lacepede). the occurrence and fate of univalent chromosomes in spermatocytes ofN. Chitala

The present report is based on the karyotype studies of two species of fishes,Notopterus chitala andN. notopterus, collected from the river Jumna, Delhi, India. Both species possess a diploid number of 48 chromosomes, 12 of which are metacentric. The primary and secondary spermatocytes of one individual ofN. chitala have been found to possess varying numbers of univalent chromosomes. The possible origin and fate of the univalents are discussed.     

Karyotype studies in thirteen species of fishes

The karyotypes of thirteen species of fishes belonging to nine families, studied in spermatogonial cells and in primary and secondary spermatocytes are reported. All these fishes were collected from the river Jumna near Delhi (India). The diploid number of chromosomes of these species ranges between 86 (Wallago attu) and 40 (Ompak bimaculatus). The karyotypes of seven species are characterized by exclusively possessing acrocentric chromosomes, while the remaining six species have varying numbers of metacentric chromosomes in addition to acrocentric chromosomes. Species belonging to the same family, and even the same genus, have been found to differ in chromosome number and morphology.On the basis of the data available, the author has endeavoured to discuss the relationship between cytologically known fish species and the various complications involved in their classification. The validity of the nombre fondamental hypothesis of Matthey in fish karyotypes has also been discussed.     

Post-pollination biochemical changes in the floral organs of<Emphasis Type="Italic">Rhynchostylis retusa</Emphasis> (L.) Bl. and<Emphasis Type="Italic">Aerides multiflora</Emphasis> Roxb. (Orchidaceae)

If left unpollinated, the flowers ofAerides multiflora (Roxb.) andRhynchostylis retusa (L.) Bl. can remain fresh for 17 and 24 d, respectively. However, they begin to wilt at 2 to 3 days after pollination (DAP) and 3 to 4 DAP, respectively, and become senescent at 5 DAP and 7 DAP, respectively. When measured at two developmental phases — Stage 1, start of wilting and Stage 2, progression to senescence — all the floral organs from pollinated flowers had higher contents of total soluble sugars, reducing sugars, and free amino acids than those from unpollinated flowers. A corresponding increase was noted in the activities of hydrolytic enzymes, i.e., α-amylase, β-amylase, and invertase, and proteolytic enzymes (proteases) in those organs. This indicated that signals related to pollination had up-regulated those activities, leading to a breakdown of complex molecules into simpler ones for mobilization. The amounts of sugars and enzyme activity were relatively greater in the pollinated flowers ofA. multiflora compared withR. retusa, and levels were always higher in the floral lips and perianths. When inhibitors of auxin (0.25 mM TIBA) or ethylene (0.25 mM AgNO₂) were applied to the pollinated flowers, their senescence was partially prevented, thus signifying hormonal involvement in governing the pollination-induced biochemical alterations normally found in those organs.     

Induction of prolonged asthma tolerance by IL-10-differentiated dendritic cells: differential impact on airway hyperresponsiveness and the Th2 immunoinflammatory response

IL-10-differentiated dendritic cells (DC10s) can prevent allergen sensitization and reverse the asthma phenotype in mice with established disease. However, little is known about the time-frames over which this tolerance is effective. We report that at 2 wk after i.p. or transtracheal delivery of 1 × 10(6) OVA-, but not house dust mite- presenting, DC10s to OVA-asthmatic mice, significant diminution of airway hyperresponsiveness (AHR) was first apparent, whereas AHR was abrogated between 3 and 10 wk posttreatment. At 13 wk, AHR returned to pretreatment levels but could again be reversed by DC10 retreatment. The impact of a single DC10 treatment on airway eosinophil and Th2 cytokine responses to recall OVA challenge, and on OVA-specific IgE/IgG1 responses, was substantial at 3 wk posttreatment, but progressively increased thereafter, such that at 8 mo, airway eosinophil and Th2 responses to recall allergen challenge remained ～85-95% suppressed relative to saline-treated asthmatic mice. Four biweekly DC10 treatments, whether transtracheal or i.p., reduced all asthma parameters to near background by 8 wk, whereas s.c. DC10 treatments did not affect AHR but did reduce the airway Th2 responses (i.v. DC10 had no discernible effects). Repeated challenge of the DC10-treated mice with aerosolized OVA (100 μg/ml) did not reverse tolerance, but treatment with the indoleamine-2,3-dioxygenase antagonist 1-methyltryptophan or neutralizing anti-IL-10R from days 12 to 21 after DC10 therapy partially reversed tolerance (Th2 cytokine responses, but not AHR). These findings indicate that DC10-induced Th2 tolerance in asthmatic animals is long lived, but that DC10s employ distinct mechanisms to affect AHR versus Th2 immunoinflammatory parameters.     

Promotion of Growth in Mungbean (Phaseolus aureus Roxb.) by Selenium is Associated with Stimulation of Carbohydrate Metabolism

The mungbean plants were grown hydroponically in the absence (control) or presence of 0.1, 0.25, 0.50 and 0.75 ppm selenium (as sodium selenate) for 10 days. The growth of shoots and roots increased with application of selenium with greater extent in shoots. With 0.5 and 0.75 ppm Se levels, the shoot growth was stimulated by 24% to 27% over control, respectively, while the roots showed a corresponding increase of 18-19%, respectively. The shoot-to-root ratio was enhanced significantly with Se application and maximum effects occurred at 0.75 ppm Se. A significant increase was observed in chlorophyll and cellular respiration ability with 0.5 and 0.75 ppm selenium. The increase in growth by selenium was accompanied by elevation of starch, sucrose and reducing sugars. The activity of starch hydrolysing enzymes--amylases and sucrose hydrolysing enzyme--invertase was stimulated significantly with selenium. This was associated with elevation of activities of sucrose synthesising enzymes--sucrose synthase and sucrose phosphate synthase. It was concluded that increase in growth of shoots and roots by application of Se was possibly the result of up-regulation of enzymes of carbohydrate metabolism thus providing energy substrates for enhanced growth.