Diastereoselective synthesis of novel spiro indanone fused pyrano[3,2-c]chromene derivatives following hetero-Diels–Alder reaction and in vitro anticancer studies

The development of concise methods for the synthesis of small functionalised spirocyclic molecules is important in the search of new bioactive molecules. To contribute this, here we represent a diastereoselective oxa-hetero-Diels–Alder reaction for the synthesis of novel spiro indanone fused pyrano[3,2-c]chromene derivatives and studied their in vitro anticancer activities. Using previously less explored cyclic ketone i.e. indane-1,3-dione and 3-vinyl-2H-chromene derivatives, we obtained novel spiro-heterocyclic frameworks at the interphase between “drug-like” molecules and natural products. Various spiro indanone fused pyrano[3,2-c]chromene derivatives were synthesized regiospecifically bearing a quaternary stereocenter in high yields (up to 85%) with excellent diastereoselectivity in toluene using 4 Å MS as additive under reflux condition at 120 °C. In vitro cytotoxic studies of these compounds against MCF-7 (breast cancer), HCT-116 (colon cancer), H-357 (oral cancer), MD-MB-231(Breast cancer) cell lines were evaluated by MTT {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide} assay in vitro. The screening results revealed that many of the compounds are showing moderate to high levels of anticancer activities against the tested cancer cell lines and some displayed potent inhibitory activities in comparison to the commercial anticancer drug 5-fluorouracil (5-FU). Among the series, compound 3′c showed most potent cytotoxicity (15.0–27.5 μM) in three cancer cell lines (MCF-7, HCT-116 and MD-MB-231).

Synthesis of novel spiro indanone fused pyrano[3,2-c]chromene derivatives following hetero-Diels–Alder reaction has been demonstrated and evaluated for their in vitro anticancer activity.     

Raised serum thiobarbituric acid reactive substance levels in malaria

To study the extent of serum lipid peroxidation in malaria, 62 patients of falciparum malaria (18 uncomplicated and 44 complicated), 15 patients of vivax malaria and 25 healthy controls were enrolled in this study. The extent of serum lipid peroxidation was evaluated by estimating serum thiobarbituric acid reactive substances (TBARS) colorimetrically. The mean serum TBARS levels were 1.5 +/- 0.29, 1.21 +/- 0.2 and 3.58 +/- 1.35 nmol/ml in controls, vivax malaria and falciparum malaria patients respectively. The TBARS level was significantly more in complicated falciparum malaria patients (4.2 +/- 1.03 nmol/ml) than uncomplicated falciparum malaria patients (2.01 +/- 0.61 nmol/ml). The TBARS level was also more in patients who died (4.82 +/- 0.64 nmol/ml) when compared to the survivors (2.92 +/- 1.05 nmol/ml).     

Comparative analysis of the large fragment of the 5′ untranslated region (LF-5′ UTR) of serotype A foot-and-mouth disease virus field isolates from India

India is endemic for foot-and-mouth disease (FMD) and in recent years a unique group within serotype A, carrying a codon deletion at an antigenically critical site in capsid protein VP3 has emerged (VP3⁵⁹-deletion group). This tempted us to analyze the noncoding region, which is an under represented area, though critically associated with virus biology and pathogenesis. Analysis of the large fragment of 5′ untranslated region (LF-5′ UTR) of type A FMD virus revealed discrepancy in the overall tree topology between LF-5′ UTR and 1D region possibly due to independent evolution of coding and noncoding regions. The VP3⁵⁹-deletion group maintained its phylogenetic distinctness even at the LF-5′ UTR. Eighteen lineage specific signatures detected here support independent evolutionary paths for the lineages. Extensive deletions of 45 and 89 nucleotides corresponding to the pseudoknot region were noticed. Conservation pattern in the ‘A₂₅₃AACA’ motif in the cre/bus stem-loop indicates the importance of first three ‘A’ residues in VPg uridylylation. Of the three polypyrimidine tract binding protein (PTB) binding sites mapped on the internal ribosome entry site (IRES), the pyrimidine tract (Py tract) in the loop of domain 2 was found to be maximally conserved and it might be the major PTB binding site. Strikingly, a deletion group lineage specific transversion was noticed in the Py tract at the 3′ end of IRES without significantly affecting its in vitro infectious titer. Hence, we presume that for efficient cap-independent viral translation, either a minimum number of pyrimidine residues rather than a complete Py tract or a Py tract tolerating transversions only at specific locations and a core motif ‘CUUU’ within the Py tract is essential.     

Determination of relationships among non-toxigenic Vibrio cholerae O1 biotype El Tor strains from housekeeping gene sequences and ribotype patterns

Sequencing of three housekeeping genes, mdh, dnaE and recA, and ribotyping for seven non-toxigenic Vibrio cholerae O1 strains isolated from different geographic sources indicate a phylogenetic relationship among the strains. Results of MLST and ribotyping indicate a clear difference between three toxigenic strains (N16961, O395, and 569B) and three non-toxigenic strains from India (GS1, GS2, and GW87) and one Guam strain (X392), the latter of which were similar in both MLST and ribotyping, while two other non-toxigenic strains from the USA and India (2740-80 and OR69) appeared to be more closely related to toxigenic strains than to non-toxigenic strains, although this was not supported by ribotyping. These results provide clues to the emergence of toxigenic strains from a non-toxigenic progenitor by acquisition of virulence gene clusters. Results of split decomposition analysis suggest that widespread recombination occurs among the three housekeeping genes and that recombination plays an important role in the emergence of toxigenic strains of V. cholerae O1.     

Gonadal dysgenesis with no uterus or vagina in a female. A case report.

An 18-year-old girl presented with primary amenorrhea and absence of secondary sexual characteristics. She had gonadal dysgenesis, clitoromegaly, absence of the vagina and a 46,XY chromosome pattern.     

Prevalence of human immunodeficiency virus infection in and around Varanasi, Uttar Pradesh, India

Human Immunodeficiency Virus (HIV) infection is rising rapidly in the eastern Uttar Pradesh; however no data is available regarding its positivity rate. We have screened 1239 cases of various groups. HIV seropositivity rate of 0.28% was noted. These results suggest that HIV infection is spreading rapidly in this part of the country. M. tuberculosis was the commonest co-infection amongst them (29.5%). We recommend routine HIV screening of all patients of tuberculosis, especially if the persons frequent the cities, visit foreign countries where sex tourism is encouraged or stay away from their spouses for long periods as true history of sexual contact with commercial sex workers was difficult to obtain from them.     

Tinea pedis — a penalty of civilization A sample survey of rural and urban population

Untersuchungen von Land- und Stadtbewohnern in Indien zeigten, daß Tinae pedis auf dem Lande praktisch nicht vorkommt, jedoch bei-3 % der Stadtbewohner. Die Schuhe spielen dabei eine große Rolle. Die Pilze können anscheinend zwischen den Zehen verschieden lang verweilen, ohne dort klinische Erscheinungen zu verursachen.