Identifying appropriate prediction models for estimating hourly temperature over diverse agro-ecological regions of India.

The present study tests the accuracy of four models in estimating the hourly air temperatures in different agroecological regions of the country during two major crop seasons, kharif and rabi, by taking daily maximum and minimum temperatures as input. These methods that are being used in different crop growth simulation models were selected from the literature. To adjust the biases of estimated hourly temperature, three bias correction methods (Linear regression, Linear scaling and Quantile mapping) were used. When compared with the observed data, the estimated hourly temperature, after bias correction, is reasonably close to the observed during both kharif and rabi seasons. The bias-corrected Soygro model exhibited its good performance at 14 locations, followed by the WAVE model and Temperature models at 8 and 6 locations, respectively during the kharif season. In the case of rabi season, the bias-corrected Temperature model appears to be accurate at more locations (21), followed by WAVE and Soygro models at 4 and 2 locations, respectively. The pooled data analysis showed the least error between estimated (uncorrected and bias-corrected) and observed hourly temperature from 04 to 08 h during kharif season while it was 03 to 08 h during the rabi season. The results of the present study indicated that Soygro and Temperature models estimated hourly temperature with better accuracy at a majority of the locations situated in the agroecological regions representing different climates and soil types. Though the WAVE model worked well at some of the locations, estimation by the PL model was not up to the mark in both kharif and rabi seasons. Hence, Soygro and Temperature models can be used to estimate hourly temperature data during both kharif and rabi seasons, after the bias correction by the Linear Regression method. We believe that the application of the study would facilitate the usage of hourly temperature data instead of daily data which in turn improves the precision in predicting phenological events and bud dormancy breaks, chilling hour requirement etc.

Pest scenario of Helicoverpa armigera (Hub.) on pigeonpea during future climate change periods under RCP based projections in India.

Gram pod borer, Helicoverpa armigera (Hub.) is the major insect pest of pigeonpea and prediction of number of generations (no. of gen.) and generation time (gen. time) using growing degree days (GDD) approach during three future climate change periods viz., Near (NP), Distant (DP) and Far Distant (FDP) periods at eleven major pigeonpea growing locations of India was attempted. Multi-model ensemble of Maximum (Tmax) and Minimum (Tmin) temperature data of four Representative Concentration Pathways viz., RCP 2.6, 4.5, 6.0 and 8.5 of Coupled Model Inter comparison Project 5 (CMIP5) models was adopted here. The increase in projected Tmax and Tmin are significant during 3 climate change periods (CCPs) viz., the NP, DP and FDP over base line (BL) period under four RCP scenarios at all locations and would be higher (4.7-5.1 °C) in RCP 8.5 and in FDP. More number of annual (10-17) and seasonal (5-8) gens. are expected to occur with greater percent increase in FDP (8 to 38%) over base line followed by DP (7 to 22%) and NP (5to 10%) periods with shortened annual gen. time (4 to 27%) across 4 RCPs. The reduction of crop duration was substantial in short, medium and long duration pigeonpeas at all locations across 4 RCPs and 3 CCPs. The seasonal no.of gen. is expected to increase (5 to 35%) with shortened gen. time (4 to 26%) even with reduced crop duration across DP and FDP climate periods of 6.0 and 8.5 RCPs in LD pigeonpea. More no. of gen. of H. armigera with reduced gen. time are expected to occur at Ludhiana, Coimbatore, Mohanpur, Warangal and Akola locations over BL period in 4 RCPs when normal duration of pigeonpeas is considered. Geographical location (66 to 72%), climate period (11 to 19%), RCPs (5-7%) and their interaction (0.04-1%) is vital and together explained more than 90% of the total variation in future pest scenario. The findings indicate that the incidence of H. armigera would be higher on pigeonpea during ensuing CCPs in India under global warming context.

Evaluating area-specific adaptation strategies for rainfed maize under future climates of India.

This study investigates the spatio-temporal changes in maize yield under projected climate and identified the potential adaptation measures to reduce the negative impact. Future climate data derived from 30 general circulation models were used to assess the impact of future climate on yield in 16 major maize growing districts of India. DSSAT model was used to simulate maize yield and evaluate adaptation strategies during mid (2040-69) and end-centuries (2070-99) under RCP 4.5 and 8.5. Genetic coefficients were calibrated and validated for each of the study locations. The projected climate indicated a substantial increase in mean seasonal maximum (0.9-6.0 °C) and minimum temperatures (1.1-6.1 °C) in the future (the range denotes the lowest and highest change during all the four future scenarios). Without adaptation strategies, climate change could reduce maize yield in the range of 16% (Tumkur) to 46% (Jalandhar) under RCP 4.5 and 21% (Tumkur) to 80% (Jalandhar) under RCP 8.5. Only at Dharwad, the yield could remain slightly higher or the same compared to the baseline period (1980-2009). Six adaptation strategies were evaluated (delayed sowing, increase in fertilizer dose, supplemental irrigation, and their combinations) in which a combination of those was found to be effective in majority of the districts. District-specific adaptation strategies were identified for each of the future scenarios. The findings of this study will enable in planning adaptation strategies to minimize the negative impact of projected climate in major maize growing districts of India.

Pest scenario of Spodoptera litura (Fab.) on groundnut under representative concentration pathways (RCPs) based climate change scenarios.

Multi-model ensemble of Maximum (Tmax) and Minimum (Tmin) temperature data of four Representative Concentration Pathways viz., RCP 2.6, RCP 4.5, RCP 6.0 and RCP 8.5 of Coupled Model Intercomparison Project 5 (CMIP5) models were generated for ten major groundnut growing locations of the India to predict the number of generations of Spodoptera litura (Fab.) using Growing Degree Days approach during three future climate viz., Near (NF), Distant (DF) and Very Distant (VDF) periods and were compared over 1976-2005 baseline period (BL). Projections indicate significant increase in Tmax (0.7-4.7 °C) and Tmin (0.7-5.1 °C) in NF, DF and VDF periods under the four RCP scenarios at the ten groundnut growing locations. Higher percent increase of the number of generations of S. litura was predicted to occur in VDF (6-38%) over baseline, followed by DF (5-22%) and NF (4-9%) periods with reduction of generation time (5-26%) across the four RCP scenarios. Reduction of crop duration was higher (12-22 days) in long duration groundnut than in medium and short duration groundnut. Decrease in crop duration was higher in VDF (12.1-20.8 days) than DF (8.26-13.15 days) and NF (4.46-6.15 days) climate change periods under RCP 8.5 scenario. Increase in number of generations of S. litura was predicted even with altered crop duration of groundnut. Among locations, more number of generations of S. litura with reduced generation time are likely at Vridhachalam and Tirupathi locations. Geographical location (74-77%) and climate period (15-19%), together explained over 90 percent of the total variation in the number of generations and generation time of S. litura. These findings suggest that the incidence of S. litura on groundnut could be higher in future.

Correction: Synthesis and biological evaluation of pyrazolo-triazole hybrids as cytotoxic and apoptosis inducing agents.

Correction for 'Synthesis and biological evaluation of pyrazolo-triazole hybrids as cytotoxic and apoptosis inducing agents' by T. Srinivasa Reddy et al., Org. Biomol. Chem., 2015, 13, 10136-10149.

Design and synthesis of 1,2,3-triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates as tubulin polymerization inhibitors.

1,2,3-Triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates (5a-v) were designed, synthesized and evaluated for their cytotoxic potency against some human cancer cell lines like DU-145 (prostate), HeLa (cervical), MCF-7 (breast) HepG2 (liver) and A549 (lung). Preliminary results revealed that some of these conjugates like 5f and 5k exhibited significant antiproliferative effect against human breast cancer cells (MCF-7) with IC50 values of 0.60 and 0.78µM respectively. Flow cytometric analysis of the cell cycle demonstrated an increase in the percentage of cells in the G2/M phase which was further authenticated by elevation of cyclin B1 protein levels. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 5f and 5k, and western blot analysis revealed that these conjugates accumulated more tubulin in the soluble fraction. Moreover, the conjugates caused apoptosis of the cells that was confirmed by mitochondrial membrane potential and Annexin V-FITC assay. Molecular docking studies indicated that these conjugates occupy the colchicine binding site of the tubulin protein.

2-Arylaminobenzothiazole-arylpropenone conjugates as tubulin polymerization inhibitors.

A new series of 2-arylaminobenzothiazole-arylpropenone conjugates 5-6(a-r) was designed, synthesized and investigated for their cytotoxic potency against the various human cancer cell lines. Most of these conjugates exhibited cytotoxic activity and inhibited in vitro tubulin polymerization effectively. Conjugates 5d and 6d cause cell cycle blocks in the G2/M phase in HeLa cells and treatments with 5d and 6d manifested increased mRNA and protein levels of the G2/M marker, cyclin B1. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 5d and 6d. Western blot analysis revealed that these conjugates accumulate more tubulin in the soluble fraction. Moreover, the triggering of apoptotic cell death after mitotic arrest was investigated by studying their effect on Hoechst staining, mitochondrial membrane potential, ROS generation.

Indian summer heat wave of 2015: a biometeorological analysis using half hourly automatic weather station data with special reference to Andhra Pradesh.

Heat wave is a hazardous weather-related extreme event that affects living beings. The 2015 summer heat wave affected many regions in India and caused the death of 2248 people across the country. An attempt has been made to quantify the intensity and duration of heat wave that resulted in high mortality across the country. Half hourly Physiologically Equivalent Temperature (PET), based on a complete heat budget of human body, was estimated using automatic weather station (AWS) data of four locations in Andhra Pradesh state, where the maximum number of deaths was reported. The heat wave characterization using PET revealed that extreme heat load conditions (PET >41) existed in all the four locations throughout May during 2012-2015, with varying intensity. The intensity and duration of heat waves characterized by "area under the curve" method showed good results for Srikakulam and Undi locations. Variations in PET during each half an hour were estimated. Such studies will help in fixing thresholds for defining heat waves, designing early warning systems, etc.

Synthesis and biological evaluation of cis-restricted triazole/tetrazole mimics of combretastatin-benzothiazole hybrids as tubulin polymerization inhibitors and apoptosis inducers.

A series of colchicine site binding tubulin inhibitors were synthesized by the modification of the combretastatin pharmacophore. The ring B was replaced by the pharmacologically relevant benzothiazole scaffolds, and the cis configuration of the olefinic bond was restricted by the incorporation of a triazole and tetrazole rings which is envisaged by the structural resemblance to a tubulin inhibitor like combretastatin (CA-4). These compounds were evaluated for their antiproliferative activity on selected cancer cell lines and an insight in the structure activity relationship was developed. The most potent compounds (9a and 9b) demonstrated an antiproliferative effect comparable to that of CA-4. Mitotic cell cycle arrest in G2/M phase revealed the disruption of microtubule dynamics that was confirmed by tubulin polymerization assays and immunocytochemistry studies at the cellular level. Western blot analysis revealed that these compounds accumulate more tubulin in the soluble fraction. The colchicine competitive binding assay and the molecular docking studies suggested that the binding of these mimics at the colchicine site of the tubulin is similar to that of CA-4. Moreover, the triggering of apoptotic cell death after mitotic arrest was investigated by studying their effect by Hoechst staining, Annexin-V-FITC assay, mitochondrial membrane potential, ROS generation and caspase-3 activation.

Synthesis and biological evaluation of imidazopyridinyl-1,3,4-oxadiazole conjugates as apoptosis inducers and topoisomerase IIα inhibitors.

A series of imidazopyridinyl-1,3,4-oxadiazole conjugates were synthesized and investigated for their cytotoxic activity and some compounds showed promising cytotoxic activity. Compound 8q (NSC: 763639) exhibited notable growth inhibition that satisfies threshold criteria at single dose (10µM) on all human cancer cell lines. This compound was further evaluated at five dose levels (0.01, 0.1, 1, 10 and 100µM) to obtain GI50 values ranging from 1.30 to 5.64µM. Flow cytometric analysis revealed that compound 8q arrests the A549 cells in sub G1 phase followed by induction of apoptosis which was further confirmed by Annexin-V-FITC, Hoechst nuclear staining, caspase 3 activation, measurement of mitochondrial membrane potential and ROS generation. Topo II mediated DNA relaxation assay results showed that conjugate 8q could significantly inhibit the activity of topo II. Moreover, molecular docking studies also indicated binding to the topoisomerase enzyme (PDBID 1ZXN).

Synthesis and biological evaluation of pyrazolo-triazole hybrids as cytotoxic and apoptosis inducing agents.

A series of pyrazolo-triazole hybrids were designed and synthesized by combining the 1,3-diphenyl pyrazole and triazole scaffolds to obtain (1-benzyl-1H-1,2,3-triazol-4-yl)(1,3-diphenyl-1H-pyrazol-4-yl)methanones. All the synthesized compounds were screened for their anticancer activity against four tumor cell lines, viz. HT-29 (colon), PC-3 (prostate), A549 (lung), and U87MG (glioblastoma) cells. Most of the tested compounds showed moderate to potent cell growth inhibition on different cancer cells, in particular, the compounds 17, 23, and 29 exhibited promising cytotoxicity against these cell lines with the IC50 values in the range of 0.86-3.72 µM. In addition, the potential mechanism of cell growth inhibition and apoptotic induction by these compounds was investigated in U87MG cancer cells using cell-based assays, including wound healing assay, flow cytometry, Hoechst staining, acridine orange/ethidium bromide staining, Annexin V-FITC/propidium Iodide dual staining, Rhodamine 123 staining, and carboxy-DCFDA staining. The results indicate that the compounds induce apoptosis in U87MG cells via mitochondrial pathway through up-regulation of pro-apoptotic (Bax) and down-regulation of anti-apoptotic (Bcl-2) genes. Based on these studies, three compounds 17, 23 and 29 have been identified as promising new molecules that have the potential to be developed as leads.

Synthesis of 2-aryl-1,2,4-oxadiazolo-benzimidazoles: Tubulin polymerization inhibitors and apoptosis inducing agents.

A new series of 2-aryl 1,2,4-oxadiazolo-benzimidazole conjugates have been synthesized and evaluated for their antiproliferative activity in the sixty cancer cell line panel of the National Cancer Institute (NCI). Compounds 5l (NSC: 761109/1) and 5x (NSC: 761814/1) exhibited remarkable cytotoxic activity against most of the cancer cell lines in the one dose assay and were further screened at five dose concentrations (0.01, 0.1, 1, 10 and 100 µM) which showed GI50 values in the range of 0.79-28.2 µM. Flow cytometric data of these compounds showed increased cells in G2/M phase, which is suggestive of G2/M cell cycle arrest. Further, compounds 5l and 5x showed inhibition of tubulin polymerization and disruption of the formation of microtubules. These compounds induce apoptosis by DNA fragmentation and chromatin condensation as well as by mitochondrial membrane depolarization. In addition, structure activity relationship studies within the series are also discussed. Molecular docking studies of compounds 5l and 5x into the colchicine-binding site of the tubulin, revealed the possible mode of interaction by these compounds.

Synthesis of 2-anilinopyridyl-triazole conjugates as antimitotic agents.

A series of 2-anilinopyridyl­triazole conjugates (6a­t) were prepared and evaluated for their cytotoxic activity against a panel of three human cancer cell lines. Among them compounds 6q, 6r and 6s showed significant cytotoxic activity with IC50 values ranging from 0.1 to 4.1 µM. Structure­activity relationships were elucidated with various substitutions on these conjugates. Flow cytometric analysis revealed that these compounds arrest the cell cycle at the G2/M phase and induce cell death by apoptosis. The tubulin polymerization assay and immunofluorescence analysis showed that these compounds (6q, 6r and 6s) effectively inhibited the microtubule assembly in human prostate cancer cells (DU-145). The docking studies showed that 6s interacts and binds efficiently with the tubulin protein at the colchicine binding site. This was further confirmed by the colchicine competitive binding assay. Moreover, compounds 6q, 6r and 6s possess anti-tubulin activity both in vitro and within cells as demonstrated by the ratio of soluble versus polymerized tubulin. Further the apoptotic effects of compounds were confirmed by Hoechst staining, caspase 3 activation, annexin-V FITC, mitochondrial membrane potential and DNA fragmentation analysis. Interestingly, these compounds did not affect the normal human embryonic kidney cells, HEK-293.

Synthesis and biological evaluation of podophyllotoxin congeners as tubulin polymerization inhibitors.

A series of new podophyllotoxin derivatives containing structural modifications at C-7, C-8, and C-9 were synthesized and evaluated for their cytotoxic activity against three human cancer cell lines. All the synthesized compounds showed significant growth inhibition with GI50 values in micromolar levels while some of the compounds were several times more potent against MCF-7 and HeLa cell lines than MIAPACA cell line. Three compounds (12a, 12d and 12e) emerged as potent compounds with broad spectrum of cytotoxic activity against all the tested cell lines with GI50 values in the range of 0.01-2.1 µM. These compounds induce microtubule depolymerization and arrests cells at the G2/M phase of the cell cycle. Moreover, compounds 12d and 12e disrupted microtubule network and accumulated tubulin in the soluble fraction in a similar manner to their parent podophyllotoxin scaffold. In addition, structure activity relationship studies within the series were also discussed. Molecular docking studies of these compounds into the colchicine-binding site of tubulin, revealed possible mode of inhibition by these compounds.

Synthesis and evaluation of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)nicotinamides as potential anticancer agents that inhibit tubulin polymerization.

A series of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)nicotinamides (4) was synthesized and tested for their anticancer activity against a panel of 60 human cancer cell lines. Some of the representative compounds such as 4a, 4b, 4f, 4g, 4i and 4t were selected for the five dose study and amongst them 4g and 4i displayed significant anticancer activity with GI50 values ranging from 0.25 to 8.34 and 1.42 to 5.86µM, respectively. Cell cycle analysis revealed that these compounds induced cell cycle arrest at G2/M phase in MCF-7 cells. The most active compound in this series 4g also inhibited tubulin polymerization with IC50 value 1.93µM superior to that of E7010. Moreover, assay to investigate the effect on caspase-9, Hoechst staining and DNA fragmentation analysis suggested that these compounds induced cell death by apoptosis. Docking experiments showed that they interact and bind efficiently with tubulin protein. Overall, the results demonstrate that N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)nicotinamide scaffold possess anticancer property by inhibiting the tubulin polymerization.

Design and synthesis of benzo[c,d]indolone-pyrrolobenzodiazepine conjugates as potential anticancer agents.

A series of benzo[c,d]indol-2(1H)one-PBD conjugates (11a-l) have been designed and synthesized as potential anticancer agents. These compounds were prepared by linking the C8-position of DC-81 with a benzo[c,d]indol-2(1H)one moiety through different alkane spacers in good yields and confirmed by (1)H NMR, mass and HRMS data. The DNA binding ability of these conjugates was evaluated by thermal denaturation studies and interestingly, compound 11l showed enhanced DNA binding ability. These compounds were also evaluated for their anticancer activity in selected human cancer cell lines of lung, skin, colon and prostate by using MTT assay method. These new conjugates showed promising anticancer activity with IC(50) values ranging from 1.05 to 36.49 µM. Moreover, cell cycle arrest in SubG1 phase was observed upon treatment of A549 cells with 1 and 2 µM (IC(50)) concentrations of compound 11l and it induced apoptosis. This is confirmed by Annexin V-FITC, Hoechst staining, caspase-3 activity as well as DNA fragmentation analysis.