Scope of organometallic compounds based on transition metal-arene systems as anticancer agents: starting from the classical paradigm to targeting multiple strategies.

The advent of the clinically approved drug cisplatin started a new era in the design of metallodrugs for cancer chemotherapy. However, to date, there has not been much success in this field due to the persistence of some side effects and multi-drug resistance of cancer cells. In recent years, there has been increasing interest in the design of metal chemotherapeutics using organometallic complexes due to their good stability and unique properties in comparison to normal coordination complexes. Their intermediate properties between that of traditional inorganic and organic materials provide researchers with a new platform for the development of more promising cancer therapeutics. Classical metal-based drugs exert their therapeutic potential by targeting only DNA, but in the case of organometallic complexes, their molecular target is quite distinct to avoid drug resistance by cancer cells. Some organometallic drugs act by targeting a protein or inhibition of enzymes such as thioredoxin reductase (TrRx), while some target mitochondria and endoplasmic reticulum. In this review, we mainly discuss organometallic complexes of Ru, Ti, Au, Fe and Os and their mechanisms of action and how new approaches improve their therapeutic potential towards various cancer phenotypes. Herein, we discuss the role of structure-reactivity relationships in enhancing the anticancer potential of drugs for the benefit of humans both in vitro and in vivo. Besides, we also include in vivo tumor models that mimic human physiology to accelerate the development of more efficient clinical organometallic chemotherapeutics.

Identification of Triticum aestivum nsLTPs and functional validation of two members in development and stress mitigation roles.

Role of plant nsLTP in biotic stress is well reported; however, their role during abiotic stress is far from clear. This study comprises genome-wide identification of LTPs and characterizes the regulation and function of two Triticum aestivum lipid transfer proteins, TaLTP40 and TaLTP75, under stresses that influence membrane fluidity. A total of 105 LTP gene family members have been identified. The selected LTPs for functional validation were highly expressed during salt, cold and drought stress. Further, selected LTPs showed differential expression thermotolerant and thermosusceptible wheat cultivars. Higher expression of many TaLTPs was observed under different abiotic stresses in thermotolerant wheat cultivars as compared to thermosusceptible cultivars. TaLTPs regulation was correlated with light energy distribution studies under similar stress conditions. Cellular localization revealed localization of different TaLTPs to the tonoplast membrane along with the organelles involved in the secretory pathway. Induction of TaLTPs was observed upon treatment with dimethylsulphoxide. TaLTP40 and TaLTP75 overexpressing transgenic Arabidopsis showed a constitutively enhanced salt tolerance. Both the TaLTP40 and TaLTP75 overexpressing lines performed better in terms of chlorophyll a fluorescence, total chlorophyll content, membrane injury index, total biomass, percentage germination, percentage survival and relative growth rate. Hence, our analyses indicate that TaLTPs expression might be driven by change in membrane fluidity and could be involved in transferring membrane lipids to the biological membranes thus imparting tolerance to various abiotic stresses.

Morpho-physiological and transcriptome profiling reveal novel zinc deficiency-responsive genes in rice.

Intensive farming has depleted the soil zinc (Zn) availability resulting in decreased crop productivity. Here, we attempt to understand the Zn deficiency response in rice through temporal transcriptome analysis. For this, rice seedlings were raised under Zn-deficient conditions up to 4 weeks followed by Zn re-supply for 3 days. Zn-deficient plants developed characteristic deficiency symptoms such as leaf bronzing, decrease in biomass, total chlorophyll, PSII efficiency, decreased carbonic anhydrase activity and increased ROS production. Interestingly, severe alterations in root system architecture were also observed. Comprehensive transcriptome analyses of rice seedlings were carried out after 2 (DEF2W) and 4 weeks (DEF4W) of Zn deficiency with respect to transcriptome profiles of corresponding Zn sufficient conditions (SUF2W, SUF4W). Additionally, to detect the potential Zn-responsive genes, transcriptome profile of Zn-recovered seedlings was compared with DEF4W. All differentially expressed Zn-responsive genes were categorized into early and late Zn deficiency response, and a set of 77 genes, induced and repressed on Zn deficiency and re-supply, respectively, was identified. These genes could be used as low Zn-responsive marker genes. Further, genes involved in membrane transport, phytosiderophore activity and organic acid biosynthesis showed high differential expression. Additionally, the present study unravelled several genes putatively associated with alterations in root system architecture under Zn deficiency and provides novel insights into the interpretation of morpho-physiological, biochemical and molecular regulation of zinc deficiency responses in rice.

Photosynthetic efficiency, temperature induction response, carbon isotope discrimination correlate with expression profiling in Indian wheat cultivars.

In the backdrop of global warming and increase in temperatures, wheat productivity worldwide would be limited. This study was therefore undertaken to analyze the heat stress response in 12 different cultivars of Indian wheat. Three developmental stages were used i.e. germination stage, seedling stage and anthesis stage, to characterize thermotolerant and thermosusceptible cultivars on the basis of different physiological and molecular parameters. Lethal temperature stress on germinating seeds showed a clear reduction in percentage germination. At the seedling stage, higher decrease in Fv/Fm, total chlorophyll content, membrane injury and carbon isotope discrimination was observed in thermosusceptible cultivars. Results similar to seedling stage were obtained at anthesis stage. PSII efficiency of late-sown cultivars and timely-sown cultivars also indicated that thermosusceptible cultivars are more prone to terminal heat stress than thermotolerant cultivars. Heat Susceptibility Index (HSI) was calculated on the basis of physiological parameters. Based on HSI, thermotolerant and thermosusceptible cultivars were identified. HSI revealed comparatively low heat susceptibility in K7903, CBW12 and C306 and high heat susceptibility in PBW343, HD2329 and HD2428. On the basis of HSI, expression analysis of stress induced genes was performed between 2 tolerant cultivars C306 and K7903 along with 2 susceptible cultivars, HD2329 and PBW343. Higher expression of stress induced genes was observed in the 2 thermotolerant cultivars C306 and K7903 as compared to the 2 thermosusceptible cultivars HD2329 and PBW343. Thus further reconfirms that stress inducible genes can be employed for categorizing cultivars into susceptible and tolerant groups.

Evaluation of Aegilops tauschii and Aegilops speltoides for acquired thermotolerance: Implications in wheat breeding programmes.

Severe and frequent heat waves are predicted in the near future having dramatic and far-reaching ecological and social impact. The aim of this study was to examine acquired thermotolerance of two Aegilops species: Aegilops tauschii and Aegilops speltoides and study their potential adaptive mechanisms. The effect of two episodes of high heat stress (45 °C/12 h) with a day of recovery period was investigated on their physiology. As compared to A. speltoides, A. tauschii suffered less inhibition of photosystem II efficiency and net photosynthetic rate (Pn). Although A. tauschii showed nearly complete recovery of PSII, the adverse effect was more pronounced in A. speltoides. Measurement of the minimum fluorescence (Fo) versus temperature curves revealed a higher inflection temperature of Fo for A. tauschii than A. speltoides, reflecting greater thermo stability of the photosynthetic apparatus. Absorbed light energy distribution revealed that A. speltoides showed increased steady state fluorescence and a lower absorbed light allocated to photosynthetic chemistry (ɸPSII) relative to A. tauschii. However, A. tauschii showed higher ability to scavenge free radicals as compared to A. speltoides. This was further validated by higher expression of ascorbate peroxidase gene. These results suggest that A. tauschii showed faster recovery and a better thermostability of its photosynthetic apparatus under severe stress conditions along with a better regulation of energy channeling of PSII complexes to minimize oxidative damage and thus retains greater capability of carbon assimilation. These factors aid in imparting a greater heat tolerance to A. tauschii as compared to A. speltoides and thus make it a better candidate for alien species introgression in wheat breeding programs for thermotolerance in wheat.