A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO3)3 as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leukemia), HepG2 (Hepatocellular carcinoma) and MCF 12A (normal epithelial breast cell line) using MTT assay, where they showed highest inhibitory activity against MCF-7. The molecules were also found to be non-toxic to MCF 12A cells. These molecules showed considerable inhibitory percentage against Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK), in in-vitro assay. Molecular docking study was carried out on the analogs and reference compound (Erlotinib) into the ATP binding site of EGFR-TK domain (PDB ID:1M17) to elucidate vital structural residues necessary for bioactivity. The effect of most active compound 7l was also estimated in-vivo in DMBA induced mammary tumor in female Sprague-Dawley rats. The effect of anti-breast cancer effect of 7l was quantified on the basis of tumour incidence, body weight and tumor volume in DMBA-induced rats. Its effect on biochemical parameters, such as antioxidant status (SOD, CAT, GPX and GSH) and lipid peroxidation was also studied. The compound 7l showed inhibition of EGFR downstream signalling in the western blot analysis.

Cystic fibrosis (CF), a monogenetic disease caused mostly by the F508del mutation, a deletion of phenylalanine at position 508 of the CF transmembrane conductance regulator (CFTR) protein, which causes improper localization and functioning of this chloride channel in lung, pancreas, and intestine by affecting the normal fluid homeostasis. In CF the lungs are the most affected organ due to the accumulation of thick mucus, which results into heavy bacterial load and associated chronic inflammation. Therefore, novel state-of-the-art therapies are needed to circumvent this problem. To address this, a series of compounds (thiazolidin-4-one-1,3,5triazines) was tested for the inhibition of NF-κB, and compounds SP6 and SP5 showed most significant activity (respectively with relative NF-ĸB activity: 1.82 ± 1.87 and 1.96 ± 1.56). Docking studies of the active compounds in the DNA binding surface of the N-terminal domains of NF-ĸB were also carried out to identify which structural motifs are vital for activity. These compounds were also tested for antibiofilm activity against P. aeruginosa and S. aureus where they showed MIC ranges from 7.81-125 µg mL -1 . The most active compound -SP6 was further assayed by micro-Ussing chamber experiments to determine its CFTR inhibitory properties, given its structural similarity to CFTR Inh 172. Results suggest that SP6 does not inhibit CFTR alone or in combination with Inh 172 .

A novel series of 1,3,5-triazine-thiazolidine-2,4-diones was synthesized and characterized by a number of analytical and spectroscopic techniques.

Due to unavailability of a specific drug/vaccine to attenuate severe acute respiratory syndrome coronavirus 2, the current strategy to combat the infection has been largely dependent upon the use of anti-inflammatory drugs to control cytokines storm responsible for respiratory depression. Thus, in this study, we discovered novel pyrazole analogs as a potent nuclear factor kappa B (NF-ĸB) inhibitor. The compounds were assessed for NF-ĸB transcriptional inhibitory activity in RAW264.7 cells after stimulation with lipopolysaccharides (LPS), revealing Compound 6c as the most potent analog among the tested series. The effect of Compound 6c was further investigated on the levels of interleukin-1β, tumor necrosis factor-α, and interleukin-6 in LPS-stimulated RAW267.4 cells by enzyme immunoassay, where it causes a significant reduction in the level of these cytokines. In Western blot analysis, Compound 6c also causes the inhibition of inhibitor kappa B-α and NF-κB. It was found to be snugly fitted into the inner grove of the active site of NF-ĸB by forming H-bonds and a nonbonded interaction with Asn28 in a docking analysis.

We reviewed the geological record of mangroves based on fossil pollen, fruits, and wood evidence of Nypa, Avicennia, Sonneratia, Rhizophoraceae, and mangrove associates to trace the origin, distribution, extinction, and range contraction of paleo‐mangroves during the Late Cretaceous–Miocene time. Our study region covers paleocoastal areas of Indo‐West Pacific (IWP) and Atlantic East Pacific (AEP) region. First, we compiled the mangrove fossil records from the Late Cretaceous till Miocene and identified the migration pattern for Nypa, Avicennia, Sonneratia, Rhizophoraceae members, and mangrove associates such as Acrostichum, Wetherellia, Pelliciera, Aegiceras, Heritiera, Excoecaria, and Barringtonia. Second, we interpreted the paleoclimate shifts which caused the dispersal/extinction of this specialized ecosystem. Lastly, we proposed the future consequences of mangrove diversity for restoration and conservation strategies. First mangroves appeared during the Late Cretaceous, 100–65 Ma, since then their evolution is closely related to sea‐level changes in geological times. The oldest geological record of Nypa palm which prefers broad ecological tolerance is a good example for pantropical distribution of mangroves. High sea‐level and humid climate offered sufficient coastal regions and climate for the development of 12 genera of mangroves in nine families and subsequent proliferation into newer areas during early to middle Eocene (~50–40 Ma). The Eocene/Oligocene boundary crisis heralds the beginning of a biogeographical split between the present‐day eastern and western provinces of mangroves with records of Sonneratia, Rhizophora, Pelliciera, Barringtonia, and Acrostichum. However, during Oligocene and Middle Miocene mangroves occupied the present geographical position with addition of Nypa, Avicennia, and Excoecaria species. Re‐evaluation of Cenozoic records suggests that the climatic conditions of Late Paleocene, end of Eocene, and middle Pliocene were the driving force that led to the evolution and expansion of mangrove flora. During the Neogene, latitudinal contraction, extinction, and migration of mangroves led to the present bipartite distribution. The Himalayan uplift and establishment of Asian summer monsoon toward Late Neogene further affected the coastal dynamics which tailored the mangrove distribution of the Indian subcontinent. Loss of ecological habitats and local extinction forming disjunct distribution of mangroves during the Quaternary have also affected its overall biogeography.

Abstract. Industrial and transport activities are the two major sources of noise pollution in any metropolitan city. Lucknow city, the capital of the largest populated state Uttar Pradesh in India has an area of 310 sq. km and is rapidly growing as a commercial, industrial and trading centre of northern India. Th e population of Lucknow city as per census 2001 is 22.45 Lacs. It is expected that by the year 2021 it will make 45 Lacs. Th e total vehicle population in Lucknow city on 31 March 2008, was nearly 1 million with almost 80% two wheelers, 12% cars, 1.36% three wheelers, 0.45% buses etc. A study was carried out to assess the existing status of noise levels and its impacts on the environment with a possibility of further expansion of the city. Ambient noise levels were measured at diff erent locations selected on the basis of land use such as silence, heavy traffi c and residential and commercial zones. It was found that noise levels at all selected locations were much higher (75-90 dB) than the prescribed limits. Th e observed traffi c volume and data on road geometry were used to predict noise levels using Federal Highway Administration Agency (FHWA) model and the calculated noise levels were compared with the observed levels for checking the suitability of this model for predicting the future levels. It was established that the results obtained by FHWA model were very close to the observed noise levels and that the model was suitable to be used for other similar metropolitan cities in India.

No abstract

Parkinson's disease (PD) is a chronic neuro‐degenerative ailment characterized by impairment in various motor and nonmotor functions of the body. In the past few years, adenosine A2A receptor (A2AR) antagonists have attracted much attention due to significant relief in PD. Therefore, in the current study, we intend to disclose the development of novel 1,3,5‐triazines as A2AR antagonist. The radioligand binding and selectivity of analogs were tested in HEK293 (human embryonic kidney) and the cells were transfected with pcDNA 3.1(+) containing full‐length human A2AR cDNA and pcDNA 3.1(+) containing full‐length human A1R cDNA, where they exhibit selective affinity for A2AR. Molecular docking analysis was also conducted to rationalize the probable mode of action, binding affinity, and orientation of the most potent molecule (7c) at the active site of A2AR. It has been shown that compound 7c form numerous nonbonded interactions in the active site of A2AR by interacting with Ala59, Ala63, Ile80, Val84 Glu169, Phe168, Met270, and Ile274. The study revealed 1,3,5‐triazines as a novel class of A2AR antagonists.