Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics
Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that cause millions of deaths every year. With the new understanding of the molecular mechanism(s) of disease progression, our knowledge about the disease is snowballing, leading to the evolution of many new therapeutic regimes and their successive trials. In the past few decades, various combinations of therapies have been proposed and are presently employed in the treatment of diverse cancers. Targeted drug therapy, immunotherapy, and personalized medicines are now largely being employed, which were not common a few years back. The field of cancer discoveries and therapeutics are evolving fast as cancer type-specific biomarkers are progressively being identified and several types of cancers are nowadays undergoing systematic therapies, extending patients’ disease-free survival thereafter. Although growing evidence shows that a systematic and targeted approach could be the future of cancer medicine, chemotherapy remains a largely opted therapeutic option despite its known side effects on the patient’s physical and psychological health. Chemotherapeutic agents/pharmaceuticals served a great purpose over the past few decades and have remained the frontline choice for advanced-stage malignancies where surgery and/or radiation therapy cannot be prescribed due to specific reasons. The present report succinctly reviews the existing and contemporary advancements in chemotherapy and assesses the status of the enrolled drugs/pharmaceuticals; it also comprehensively discusses the emerging role of specific/targeted therapeutic strategies that are presently being employed to achieve better clinical success/survival rate in cancer patients.
Anand, Uttpal; Dey, Abhijit; Chandel, Arvind K. Singh; Sanyal, Rupa; Mishra, Amarnath; Pandey, Devendra Kumar; De Falco, Valentina; Upadhyay, Arun; Kandimalla, Ramesh; Chaudhary, Anupama; Dhanjal, Jaspreet Kaur; Dewanjee, Saikat; Vallamkondu, Jayalakshmi; Pérez De La Lastra, José M.
A new cavernicolous assassin bug from the Canary Islands (Hemiptera: Reduviidae: Emesinae: Collartidini)
The Canary Archipelago is home to two species of obligately cavernicolous assassin bugs of the genus Collartida Villiers, 1949 (Hemiptera: Heteroptera: Reduviidae: Emesinae: Collartidini). These species are highly adapted for cave life, being blind and wingless. In the present study, we describe a new species of the genus, C. phantasma sp. nov. from the Federica mine in Gran Canaria. C. phantasma sp. nov. differs from the other two Collartida species found in the Canary Archipelago in that the male is fully winged, the female is wingless, and both sexes have well-developed eyes. We provide information regarding the new species’ habitat, its taxonomic affinities, and its ability to fly.
Davranoglou, Leonidas-Romanos; Baňař, Petr; Suárez, Daniel; Martín, Sonia; Naranjo, Manuel.
Mapping stressed wheat plants by soil aluminum efect using C‑band SAR images: implications for plant growth and grain quality
Under toxic aluminum (Al) levels in the soil, wheat (Triticum aestivum L.) sufers stress and plant growth is afected. A method for diagnosis of plants is proposed that includes the following as a strategy: to analyze total Al in the soil, employ satellite radar imagery and calculate a vegetation index. The objective of this research, conducted at the feld scale, was to explore how radar backscattering coefcients from a winter wheat canopy, combined with the normalized diference vegetation index (NDVI) and geographic information system (GIS) technology, can be used as a mapping tool for the variability of Al-stressed canopies. As a result, an analysis of covariance showed signifcant diferences, and the lowest plant height was obtained at a high level of soil Al, as well as the minimum grain weight and magnesium content. It was found that a simple model could be used to estimate plant height from the backscattering coefcient of vertical transmit-vertical receive polarization (σ°VV), with a strong correlation (r−0.84). In turn, a third-order polynomial regression model (R20.70) was proposed to estimate the NDVI from σ°VV. This model provided a good estimate of the NDVI at the stem elongation stage of growth (50 days after sowing). Detected NDVI patterns were associated with variation in canopy stress depending on polarimetric information, which, in turn, was related to soil Al levels. Thus, the maps derived from the model can monitor spatial variability, where NDVI values<0.68 indicate stressed areas. This study provides guidance for in-season stress spatial variability caused by Al.
Hernández, Mercedes; Borges, Andrés A.; Francisco‑Bethencourt, Desiderio.
Cyclolauranes as plausible chemical scaffold against Naegleria fowleri
Primary amoebic meningoencephalitis (PAM) is a central nervous system (CNS) disease caused by Naegleria fowleri that mainly affects children and young adults with fatal consequences in most of the cases. Treatment protocols are based on the combination of different antimicrobial agents, nonetheless there is the need to develop new anti-Naegleria compounds with low toxicity and full effects compared to the currently used drug combination. The marine environment is a well-established source of bioactive natural products. In this work, we have focused on the structure of Laurencia cyclolaurane-type sesquiterpenes as potential chemical model against Naegleria species. The effects of debromolaurinterol (1) to induce PCD/apoptosis-like events in Naegleria fowleri have been evaluated, revealing that this compound induced reduction of ATP production showing a decrease of 99.98% in treated parasite cells. A SAR analysis have been supported with molecular modeling and analysis of the in silico ADME/Tox properties of the Laurencia sesquiterpenes debromolaurinterol (1), laurinterol (2) and allolaurinterol (3), which reinforce cyclolaurane metabolites as plausible molecular models to develop PAM treatments.
Arberas-Jiménez, Íñigo; García-Davis, Sara; Rizo-Liendo, Aitor; Sifaoui, Inés; Quintana Morales, Ezequiel; Piñero, José E.; Lorenzo-Morales, Jacob; Díaz-Marreno, Ana R.; Fernández, José J.
Proposal for structural revision of several monosubstituted tricycloalternarenes
Cycloalternarenes are a group of meroterpenes isolated from epiphytic fungi with a mono-, bi, tri- or tetracyclic skeleton. We have detected in the bibliography a series of monosubstituted tricycloalternarenes with erroneous structures. Thus, in this work we make several proposals to correct the structures of nineteen 4-hydroxy-tricycloalternarenes, TCA 6a, TCA 11a2, (2E)- and (2Z)-TCA 12a, 2H-(2E)-TCA 12a, TCAs 9a and F2, methyl nor-tricycloalternarate, TCAs K, L, S–W, X2 and tricycloalterfurenes A-C, and four 6-hydroxy-tricycloalternarenes, TCA 12b, TCA 13b, tricycloalterfurene D and TCA F3. Moreover, the graphic representation of TCA 14b and TCAs 15b–18b had been corrected. In addition, we have suggested that mono-hydroxylated tricycloalternarenes can only exist in nature substituted at the 4α- or 6β-position (4R- or 6R-configuration), which could also be explained considering biogenetic reasons. We have also determined the C-4 and C-6 configuration of several monosubstituted tricycloalternarenes, whose planar structure had been previously determined. Thus, compounds of the “series a” such as TCAs 1a-8a, 11a and ACTG-toxin H have a 4R-configuration, whilst in the “series b” TCAs 3b–7b and TCAs 9b–11b possess a 6R-configuration.
Fraga, Braulio M.; Díaz, Carmen E.
Applying Biostimulants to Combat Water Deficit in Crop Plants: Research and Debate
Climate change has increased the severity of drought episodes by further reducing precipitation in vulnerable zones. Drought induces a substantial decrease in agricultural water, reducing crop yields. Consequently, addressing water consumption can increase farmers’ profits. This work describes lab-to-field research in Zea mays, using two biostimulants: glycine betaine (GB) and Lpyroglutamic acid (PG). The biostimulant optimal dosages were selected using a hydroponic system with 20% polyethylene glycol and nursery experiments under water-deficit irrigation. The established dosages were evaluated in field trials in which irrigation was reduced by 20%. Laboratory biostimulant optimisation showed in stressed treated seedlings (GB 0.1 mM; PG 1 mM) an increased dry weight, relative growth rate and water use efficiency, reducing seedling growth loss between 65 and 85%, respectively. Field trials using a GB-optimised dosage showed an increase in plants’ growth, grain yield and flour Ca content. In addition, grain flour carbohydrate content and protein remained similar to control well-watered plants. Finally, the economic aspects of biostimulant treatments, water consumption, water sources (ground vs. desalinated) and grain biomass were addressed. Overall, GB treatment demonstrated to be a valuable tool to reduce water consumption and improve farmers’ earnings.
Jiménez-Arias, David; Hernándiz, Alba E.; Morales-Sierra, Sarai; García-García, Ana L.; García-Machado, Francisco J.; Luis, Juan C.; Borges, Andrés A.
Synthesis, Biological Evaluation, and Molecular Docking Study of 3-Amino and 3-Hydroxy-seco A Derivatives of α-Amyrin and 3-Epilupeol as Inhibitors of COX-2 Activity and NF-kB Activation
In this study, a series of novel 3-seco-A derivatives of the natural triterpenes α-amyrin (1) and 3-epilupeol (2) were synthesized by a one-pot radical scission–oxidation procedure and evaluated in vitro and in vivo for their capacity to inhibit the inflammatory process. For the in vitro studies, the trans-4-hydroxy-l-proline methyl ester derivatives (1f and 2f) were consistently effective in inhibiting NO, IL-6, and TNF-α secretion, as well as inhibition of NF-κB activation, in RAW cells stimulated by LPS. The further in vivo anti-inflammatory study revealed that the trans-4-hydroxy-l-proline methyl ester derivatives (1f and 2f), together with 1g, were the most effective in inhibiting TPA-induced edema. Interestingly, the α-amyrin derivatives were the most potent inhibitors of COX-2, but inhibited COX-1 only to some extent. The hydroxyl derivative (1c) was selective for COX-2 inhibition (66.3 ± 1.1% at 17.5 μM) without affecting the COX-1 isoform and did not present toxicity. Molecular docking studies revealed that these compounds bind with their polar region in the cavity over Arg-120, and their lipophilic part is orientated to the HEM cofactor similarly to the natural substrate arachidonic acid in the catalytic site of COX-2. These results indicated that seco-A ursane derivatives could be considered promising candidates for the future development of selective NF-κB and COX-2 inhibitors.
Romero-Estrada, Antonio; Boto, Alicia; González-Christen, Judith; Romero-Estudillo, Iván; Garduño-Ramírez, María Luisa; Said Razo-Hernández, Rodrigo; Marquina, Silvia; Maldonado-Magaña, Amalia; Columba-Palomares, María C.; Sánchez-Carranza, Jessica Nayelli; Álvarez, Laura.
Impact of Volcanic Sulfur Emissions on the Pine Forest of La Palma, Spain
In autumn 2021, the largest volcanic eruption on the island of La Palma in historic records took place. The Canary Islands are of volcanic origin and eruptions have always constituted part of their natural disturbance regime. Until recently, their impacts could not be directly observed and studied. Influence of the emission of phytotoxic gases on biodiversity and ecosystem dynamics was hitherto unknown. The recent eruption is still being intensely monitored. We used Sentinel-2 remote sensing data to analyze the spatial extent and intensity of the impact related to sulfuric emissions, aiming to understand the damage patterns in Canary pine forest. The emissions damaged 10% of that forest and affected 5.3% of the Natura 2000 protected areas. We concluded that this is largely due to the toxic effects of the enormous emissions of SO2. We found a clear correlation between the change in the normalized difference vegetation index (NDVI) and distance from the eruption. This pattern was weakly anisotropic, with stronger damage in southern directions. Counteracting effects, such as ash deposition, were largely excluded by combining NDVI change detection with tree cover density. We expect that vegetation damage will be transient. P. canariensis can resprout after forest fires, where most leaves are lost. Consequently, our assessment can serve as a reference for future ecosystem regeneration.
Wiser, Frank; Baumann, Esther; Jentsch, Anke; Medina, Félix Manuel; Meng, Lu; Nogales, Manuel; Beierkuhnlein, Carl.
Limited ecophysiological variation in the Canary Island lizard Gallotia galloti (Oudart, 1839) across an elevational range of over 3500 m (Squamata: Lacertidae)
The lacertid lizard Gallotia galloti inhabits drastically different environments on the island of Tenerife, from sea level to > 3500 m, encompassing mesic as well as extremely arid sites. To obtain a first exploratory overview of the thermophysiology of lizards in this range of environments, we experimentally inferred preferred temperature (Tpref) and instant evaporative water loss (IWL) in 63 individuals from five bioclimatically distinct sites. We found statistically significant but weak differences between individual median Tpref values across sites, without an obvious relationship to bioclimate. Considering only adult male lizards, the highest Tpref values were found at one mesic and one very arid site. IWL differences were also significantly different across sites, and this variable was positively correlated with rainfall if analysed at the level of individual lizards, a hypothesis that requires testing against more extensive data sets. It appears that G. galloti occupies an extensive range of bioclimates without heavily adjusting its thermal physiology to local conditions.
Albaladejo-Robles, Gonzalo; Rodríguez, Noemi; Rodríguez-Concepción, Benza; Nogales, Manuel; Vences, Miguel.
Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri
Naegleria fowleri is the causative agent the primary amoebic meningoencephalitis (PAM), a fatal disease in more than the 90% of the reported cases that affects the central nervous system. The amoeba infects the nasal cavity of mostly children and young adults who report previous aquatic exposure in warm water sources. The rapid progression of the disease and the lack of effective and safety therapeutic options make the search of new anti-amoebic compounds an urgent issue. In this study, twelve sesquiterpene lactones isolated from the zoanthid Palythoa aff. clavata were tested against the trophozoite stage of Naegleria fowleri. Anhydroartemorin (2) and 1(10)Z,4E,14-acetoxy-costunolide (3) showed the best anti-amoeboid activity values with IC50 23.02 ± 1.26 and 28.34 ± 6.27, respectively. In addition, the mechanisms of programmed cell death induction of these two molecules were evaluated with positive results for both compounds. Finally, a structure-activity relationship was analyzed to reveal the dependence of reactivity and lipophilicity on the biological activity. The log P values of the compounds were calculated to postulate them as good candidates to cross the blood-brain barrier, a limiting factor in the development of new anti-Naegleria treatments. Therefore, the mentioned sesquiterpene lactones could be considered as potential PAM therapeutic options in the future.
Arberas-Jiménez, Íñigo; Rizo-Liendo, Aitor; Nocchi, Nathália; Sifaoui, Inés; Chao-Pellicer, Javier; Souto, María L.; Suárez-Gómez, Blanca; DIAZ MARRERO, ANA RAQUEL ; Fernández, José J.; Piñero, José E.; Lorenzo-Morales, Jacob.