Efficient Ru-Catalyzed Electrochemical Homo- and Heterocoupling Reaction of Terminal Alkynes: Synthesis, In Vitro Anticancer Activity, and Docking Study.

With the objective to identify novel anticancer leads, herein ruthenium-catalyzed electrochemical homo- and heterocoupling reactions of terminal alkynes have been developed for the synthesis of the desired products. Among the synthesized 1,3-diynes, some of them were rigorously examined for possible in vitro anticancer activity against HeLa (human cervical cancer) and L6 normal (rat skeletal muscle) cell lines. Additionally, the docking study was also performed toward 16 ovarian cancer targets with binding affinity calculations with respect to the standard. To the best of our knowledge, this is the first scientific report on the ruthenium-catalyzed electrochemical homocoupling reaction between terminal alkynes with its in vitro anticancer and in silico docking studies.

Major chemical constituents from Illicium griffithii Hook. f. & Thoms of North East India and their cytotoxicity and antimicrobial activities.

Illicium griffithii Hook. f. & Thoms is an endemic medicinal plant of North East India found in the Eastern Himalayan region of biodiversity mega centre. Herein, chemical investigation of I. griffithii, afforded five compounds and their structures were determined through extensive use of NMR, HRMS, and FT-IR spectroscopy. The complete proton-proton, proton-carbon coupling network of compound 1 was determined using 1H-1H COSY, HSQC and NOESY NMR experiments. All the compounds were evaluated for their cytotoxic activity by MTT assay and antimicrobial activity by Agar well diffusion method. Compound 1 exhibited significant cytotoxicity activity against Lung cancer (A549) and pancreatic cancer (MIAPaCa2) cell lines with IC50 values of 15.01 ± 2.69 µg/mL and 47.77 ± 2.38 µg/mL, respectively. Further, the compound 1 exhibited good antimicrobial activities against Escherichia coli and Candida albicans with MIC 7.50 ± 0.28 µg/mL and 7.50 ± 0.86 µg/mL, respectively. The other isolated compounds along with the extracts of I. griffithii also displayed moderate anticancer and antimicrobial activities against respective strains. To the best of our knowledge, this is the first study of isolation of compounds from bark, wood, and leaf along with cytotoxicity and antimicrobial activities of I. griffithii from the North Eastern region of India and could be a potential herbal medicine in near future.

Chemical composition, antimicrobial activity and cytotoxicity of Murraya paniculata (L.) Jack leaf essential oil from Assam, India: the effect of oil on cellular morphology of micro-organisms.

Murraya paniculata (L.) Jack is commonly cultivated as ornamental plant in Assam and has been used as spice and phytomedicine traditionally for many healthcare purposes. The therapeutic potential and chemical constituents of the essential oil of M. paniculata leaf was investigated against several pathogenic microbial species and human cancer cell lines. 29 chemical compounds were identified by GC-MS analysis from the essential oil representing 97.62% of the oil. The major compound identified was caryophyllene (20.93%). Leaf essential oil exhibited promising antibacterial activity against Mycobacterium smegmatis (MIC = 4 µg/mL) and Pseudomonas aeruginosa (MIC = 4 µg/mL). Best anticancer activity of the oil was observed for HeLa cells (IC50 = 6.28 µg/mL). Further, scanning electron microscopic studies revealed that the oil kills micro-organisms with the deformation of cellular morphology on treatment of the oil. Thus, the essential oil of M. paniculata leaf can be an excellent alternative for development of new antimicrobials and anticancer chemotherapeutic agents for the pharmaceutical industries.

Anticancer and antimicrobial compounds from Croton caudatus Gieseler and Eurya acuminata DC: Two edible plants used in the traditional medicine of the Kuki tribes.

Eurya acuminata DC and Croton caudatus Gieseler are two ethno-medicinal plants used by Kuki community of North East India. From these plants, we have characterized fifteen phytochemicals (1-15) by extensive use of chromatographic and spectroscopic methods. They were also tested for in vitro cytotoxic effects against A549 and MIAPACA2 cell lines and antimicrobial activities against Mycobacterium smegmatis and Candida albicans. All compounds showed moderate activity against the MIAPACA2 cell lines. Compounds tricosan-1-ol (6), octacosanoic acid (7), ß-sitosterol (10) and (E)-dodec-3-en-1-ol (14) exhibited promising activity against A549 cell lines with IC50 of 16.72, 4.5, 4.42 and 4.5 µg/ml respectively. Further, hexatriacontan-1-ol (2) exhibited lowest MIC of 50 µg/ml against C. Albicans and henicosan-1-ol (3) at 25 µg/ml against M. smegmatis. They were also screened through docking analysis against two Phosphatidylinositol-3-Kinase nodal proteins and three feedback loop proteins of cancers. Thus, this study validates their traditional uses as herbal anticancer and antimicrobial agents.

Acid mine drainage in an Indian high-sulfur coal mining area: Cytotoxicity assay and remediation study.

Opencast mining causes significant environmental concern due to acid mine drainage (AMD) caused by the oxidation of pyrites and other sulfur-bearing minerals. The present study intends to determine the seasonal variability of AMD in the affected area of the Ledo opencast mining, the cytotoxicity of the AMD, and the AMD remediation process. The physicochemical properties of the collected samples were analyzed by using laboratory-based methods and sophisticated instrumental tools. The cytotoxicity study of AMD water was performed by using different cell lines such as normal rat muscle and human carcinoma cells. The study demonstrates that the mine water samples have high conductivity (1.30-2.49 ms cm-1) with high total dissolved solids (1068-1339 ppm) which can change the ionic composition of water. The concentration level of trace elements are also found to be higher than the permissible limit during monsoon season. A simple laboratory-based remediation process of AMD has been carried out in the current study by using size segregated pulverized limestone and the process reveals the decrease in elemental concentrations of AMD water. This study will be useful to develop a remediation technique to minimize the concentration levels of hazardous elements and ions in the AMD water.

Blue-fluorescent and biocompatible carbon dots derived from abundant low-quality coals.

Coal is one of the most abundant natural carbonaceous materials. This paper reports a novel oxidative chemical method for the synthesis of high-value carbon dots (CDs) from cheap and abundant low-quality high­sulfur coals for use in high-end applications. These CDs were synthesized by using wet-chemical ultrasonic stimulation-induced process which is environmentally facile and less drastic compared to other chemical methods of production of CDs. The sizes of the synthesized CDs from different types of coal samples were estimated to be in the range of 1-4 nm, 1-6 nm, 2-5 nm, and 10-30 nm. The quantum yield (QY) of the CDs was determined and it was found to be around 3-14%. For high-end field application, the CDs were further tested for toxicity and were reported to be safe for environmental and biological applications. The cell image analysis under the fluorescence microscope further indicated that the synthesized CDs could be used as a promising bio-compatible material for optical-imaging as well as bio-imaging. The CDs showed promising fluorescent sensing property and can be utilized as a good probe for silver ion detection/sensing. The CDs is also found to be a promising reagent for silver nanoparticles synthesis. The results provide a new avenue for large-scale synthesis of CDs.

Multicolored Protein Nanoparticles: Synthesis, Characterization, and Cell Uptake.

Synthesis, characterization, and applications of strongly fluorescent, multicolored protein nanoparticles (GlowDots) are reported here. Bovine serum albumin was cross-linked under controlled conditions to form nanoparticles, where particle size was controlled from 20 to 100 ± 10 nm by choosing appropriate reaction conditions. The absorption as well as the emission wavelengths were controlled without changing the particle size, unlike quantum dots. Each GlowDot was loaded with up to 214 ± 50 chromophores, and hence, the particles have high molar absorptivities (106 M-1 cm-1) as well as high brightness (105 to 106 M-1 cm-1). A large number of functional groups cover the particle surface and these are further functionalized to enhance cellular uptake. GlowDots that were labeled with fluorescein and functionalized with taurine, for example, were quickly taken up by HeLa, MDA-MB-231, PC3, and L6 myoblast cells, as interrogated by fluorescence imaging studies. GlowDots were biocompatible, size tunable, biodegradable, strongly fluorescent, and stable for months at room temperature, and they may serve as substitutes for quantum dots in a variety of practical applications.

Volatile Inhibitors of Phosphatidylinositol-3-Kinase (PI3K) Pathway: Anticancer Potential of Aroma Compounds of Plant Essential Oils.

BACKGROUND: Cancer is a grave health problem for the world as the global cancer burden rises to 14 million new cases with 8.2 million deaths every year which is expected to rise by 70% in the next 2 decades as reported by the WHO.These steady rises in death demand for rapid developments in anti-cancer agents. Essential oils, being natural and multi-component complex systems have recently attracted a lot of attention in this search for novel anti-cancer agents. MATERIALS AND METHODS: The pharmaceutical attributes of essential oil components, specifically focusing on their affinity towards COX, 5-LOX, AKT, MDM2, PDK1 and mTOR which defines the phosphatidylinositol-3- kinase (PI3K) pathway, were assessed. 123 compounds present in essential oils of different plants were analyzed for their drug like attributes which were then allowed to dock with PI3K dependent receptors crucial for the development of cancer malignancies. Among them, 21 compounds were filtered possessing high druglikeness with favourable metabolism offered by major cytochromeP450 isoforms. Finally, the best docked compounds with highest binding affinities were employed for building a ligand based pharmacophore. Being inhibitors of P-glycoproteins, these molecules also exhibited good absorption profiles and noncarcinogenic properties. Further from these 21, six compounds were evaluated against A549 lung cancer cells. RESULTS: The pharmacophoric feature obtained can be applied for both designing and screening moieties for active inhibitors of the phosphatidylinositol-3-kinase pathway specifically from essential oil compounds and these final 21 compounds can be further promoted to studies for anti-cancer drug development. Among these, six compounds exhibited promising inhibitory results against A549 lung cancer cells. Furthermore, immunoblotting assay confirmed the efficacy of the compounds for inhibiting mTOR and AKT enzymes which are bandmasters for downstream signaling of thePI3K pathway. CONCLUSION: Methyl nonanoate, (R)-citronellol, cis-carveol (L-carveol), 3-methyl-Cyclohexanone, 4-carene and thujopsene were finally screened for PI3K targeted anti-cancer therapies which may find direct application as inhalers or sprays against lung cancer as these compounds are highly volatile.

Antimalarial silver and gold nanoparticles: Green synthesis, characterization and in vitro study.

In the present study, we are reporting antimalarial potential of silver (AgNPs) and gold (AuNPs) nanoparticles synthesized by leaf and bark extract of Syzygium jambos (L.) Alston (Myrtaceae). AuNPs and AgNPs obtained by both the extracts were characterized using UV-vis spectroscopy, zeta potential, transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier Transform Infrared spectroscopy (FTIR). NMR and FTIR spectra indicate that the saccharides and phenolics present in the S. jambos extracts were the major contributors responsible for the synthesis and stabilization of NPs. NPs were also synthesized by chemical methods and were compared for their antiplasmodial potential against chloroquine sensitive (3D7) and resistant (Dd2) strain of Plasmodium falciparum by using 24h schizont maturation assay. AgNPs synthesized by both the extracts showed higher antiplasmodial activity than the rest. Further, NPs synthesized by S. jambos extracts have shown insignificant cytotoxicity against human cervical cancer cell line (HeLa) and rat skeletal muscle cell line (L6), which proved their biocompatibility.

Arsenic-induced instrumental genes of apoptotic signal amplification in death-survival interplay.

Arsenic is a global health concern at present and it is well reported for causing systemic toxicity. It is also well known for generation of free radical and inducing apoptosis in different cell types. Paradoxically arsenic is reported to be a susceptible carcinogen as well. There are several reports demonstrating diverse mechanism of apoptosis in different cell types. However, the universal scenario of instrumental genes and their interaction leading to amplification of apoptotic signal are yet to be completely uncovered, which is predicted here. Conventional studies on signaling pathway aided by time and concentration kinetics data are inadequate for prediction of anchored genes for apoptotic signal amplification. Therefore, expression profile-based approach is adopted. Core apoptosis related and glutathione metabolism genes in 1 and 10 µM of arsenic-treated HepG2 cells were analyzed after 12 h of incubation. An arsenic treatment of 1 µM exhibits no cell death at 12 h, whereas 10 µM arsenic treatment reveals around 50% cell death at 12 h. Results depict 28 and 44 affected genes in 1 and 10 µM arsenic-treated cells, respectively. Early initiation of apoptotic signaling is detected in no cell death regimens (at 1 µM), whereas amplified apoptotic signal is demonstrated at 50% cell death regimens (at 10 µM). Instrumental genes involved in progression of apoptosis in the concourse of cell death and survival is designated from the responsive genes common to both the condition. We predict the initiation process is fairly aided by the activation of intrinsic pathway, which is amplified via TNF signaling and extrinsic pathway. Furthermore, regulatory genes involved in interplay between apoptosis/anti-apoptosis and their interactions are demonstrated here.

Nanominerals, fullerene aggregates, and hazardous elements in coal and coal combustion-generated aerosols: An environmental and toxicological assessment.

Studies on coal-derived nanoparticles as well as nano-minerals are important in the context of the human health and the environment. The coal combustion-generated aerosols also affect human health and environmental quality aspects in any coal-fired station. In this study, the feed coals and their combustion-generated aerosols from coal-fired boilers of two tea industry facilities were investigated for the presence of nanoparticles/nano minerals, fullerene aggregates, and potentially hazardous elements (PHEs). The samples were characterized by using X-ray diffraction (XRD), Time-of-flight secondary ion mass spectroscopy (TOF-SIMS), High resolution-transmission electron microscopy/energy dispersive spectroscopy (HR-TEM/EDS) and Ultra Violet-visible spectroscopy (UV-Vis) to know their extent of environmental risks to the human health when present in coals and aerosols. The feed coals contain mainly clay minerals, whilst glass fragments, spinel, quartz, and other minerals occur in lesser quantities. The PM samples contain potentially hazardous elements (PHEs) like As, Pb, Cd and Hg. Enrichment factor of the trace elements in particulate matters (PMs) was calculated to determine their sources. The aerosol samples were also found to contain nanomaterials and ultrafine particles. The fullerene aggregates along with potentially hazardous elements were also detected in the aerosol samples. The cytotoxicity studies on the coal combustion-generated PM samples show their potential risk to the human health. This detailed investigation on the inter-relationship between the feed coals and their aerosol chemistry will be useful for understanding the extent of environmental hazards and related human health risk.