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Polyoxyethylene tallow amine (POEA) is a nonionic surfactant added to insecticide and herbicide formulations. Experimental data have been shown the toxic effects of POEA on aquatic organisms and remain to be a serious concern. In this study, total of thirty-two potential bacteria that were isolated from herbicide-contaminated soil samples showed the ability to use POEA as the sole carbon and energy source. In which, a bacterial strain LA was further investigated based on the efficiency utilization of POEA and classified as Kosakonia oryzae by the 16S rRNA gene. Response surface methodology was successfully applied to understand the interaction of distinct factors on POEA degradation by LA strain. Degradation of POEA was confirmed with UV-Visible spectrophotometric analysis and HPLC analysis. The POEA utilization mechanism was explored by target gene detection and carbon source utilization. The results indicate that strain LA has the potential to serve as an in situ candidate for bioremediation polluted by POEA.
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Polietilenoglicóis , Poluentes do Solo , Aminas , Biodegradação Ambiental , Enterobacteriaceae , Gorduras , RNA Ribossômico 16S/genética , Solo , Microbiologia do SoloRESUMO
Plant-based antiviral therapy is the current need for holistic health care management, which can be achieved through screening of phytochemicals and designing of antiviral peptides. There exist certain host's factors which are directly involved for rapid viral replication causing worldwide pandemic. A total of 177 phytochemicals from Ocimum sanctum (L.), Tinospora cordifolia (Thunb.) Miers, Cinnamomum camphora (L.) J. Presl., Allium sativum (L.), Curcuma longa (L.), and Aloe vera (L.) Burm. f. were evaluated for their affinity to all viral proteins of H1N1. Applying drug filters and keeping the threshold of such filters relative to the standards, 82 compounds were found suitable for further analysis. Consensus scoring system was used for screening top ligands from 82 compounds, which screened the top 12 compounds. Highly conserved regions (>80%) which were hydrophilic, flexible, antigenic, and also charged were screened out as potent antiviral peptides. The viral proteins were taken as the targets for the modeled peptides for protein-protein docking. Further, host-pathogen interacting network was constructed to unveil host factors involved in viral replication, from which unique protein clusters representing their involvement in viral reproduction were selected through mapping with pathway databases. Twelve compounds and five peptides were found to be highly effective against all the proteins of H1N1. Based on the uniqueness, 13 clusters of proteins were obtained which are engaged in cellular process, namely, viral reproduction, fructose-6-phosphate metabolism, nitrogen compound metabolism, biosynthesis, cellular process, oligodendrocyte development, localization, multiorganism process, primary metabolism, response to unfolded protein, metabolism, and response to protein and catabolism.
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Antivirais/farmacologia , Desenho de Fármacos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Mapas de Interação de Proteínas/efeitos dos fármacos , Sequência de Aminoácidos , Antivirais/química , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Vírus da Influenza A Subtipo H1N1/fisiologia , Simulação de Acoplamento Molecular/métodos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Mapas de Interação de Proteínas/fisiologia , Estrutura Secundária de Proteína , Estrutura Terciária de ProteínaRESUMO
Esophageal cancer is a complex disease influenced by genetic and environmental factors. Single nucleotide polymorphisms [SNPs] in non-coding regions of the genome have emerged as crucial contributors to esophageal cancer susceptibility. This review provides a comprehensive overview of the role of SNPs in non-coding regions and their association with esophageal cancer. The accumulation of SNPs in the genome has been implicated in esophageal cancer risk. Various studies have identified specific locations in the genome where SNPs are more likely to occur, suggesting a location-specific response. Chromatin conformational studies have shed light on the localization of SNPs and their impact on gene transcription, posttranscriptional modifications, gene expression regulation, and histone modification. Furthermore, miRNA-related SNPs have been found to play a significant role in esophageal squamous cell carcinoma [ESCC]. These SNPs can affect miRNA binding sites, thereby altering target gene regulation and contributing to ESCC development. Additionally, the risk of ESCC has been linked to base excision repair, suggesting that SNPs in this pathway may influence disease susceptibility. Somatic DNA segment alterations and modified expression quantitative trait loci [eQTL] have also been associated with ESCC. These alterations can lead to disrupted gene expression and cellular processes, ultimately contributing to cancer development and progression. Moreover, SNPs have been found to be associated with the long non-coding RNA HOTAIR, which plays a crucial role in ESCC pathogenesis. This review concludes with a discussion of the current and future perspectives in the field of SNPs in non-coding regions and their relevance to esophageal cancer. Understanding the functional implications of these SNPs may lead to the identification of novel therapeutic targets and the development of personalized approaches for esophageal cancer prevention and treatment.
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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.
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Lipids have received less attention than nucleic acids and proteins, which play a major role in building up the cell. They are a complex group of biomolecules varying in structure and function whose complexity can only be revealed by refining the present analytical tools. Lipogenesis is critical for tumor growth as it has been observed that FA (Fatty Acid) synthesis increases in many cancers. In this review, we have detailed the causes and concerns for considering lipids as a trademark for cancer, including other events such as mutations, epigenetic changes, chromosomal rearrangements, and hormonal stimulations. The process of biomarker development can be heightened from the critical changes observed in lipid profiling that occur in the reprogramming of lipid metabolism. The cancer alterations that occur during lipid metabolism and the expression of various genes during this process have been discussed in detail. The routes through which cancer cells source lipids for their nourishment and energy need and how FA synthesis contributes to this are discussed. The various pathways involved in the metabolism of lipid, which has the potential to be therapeutic targets, are highlighted. Also, the various driving factors critical for lipid metabolism alterations and the major role played by lipids in cancer and ways of targeting it are critically analyzed.
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Metabolismo dos Lipídeos , Neoplasias , Humanos , Ácidos Graxos/metabolismo , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Lipogênese , Biomarcadores/metabolismoRESUMO
Nanomaterials have undergone rapid development in the last few decades, galvanized by the versatility of their functional attributes and many inherent advantages over bulk materials. The state of art experimental techniques to synthesize nanoparticles (NPs) from varied sources offers unprecedented opportunities for utilization and exploration of multifaceted biological activities. Such formulations demand a preliminary understanding of the interaction between NPs and biomolecules. Most of these interactions depend on the external morphology of the NPs, like the shape, size, charge and surface chemistry. In addition, most experimental techniques are limited to cellular-level data, without the atomistic details of mechanisms that lead to these interactions. Consequently, recent studies have determined these atomistic events through in-silico techniques, which provide a better understanding and integrative details of interactions between biomolecules and different NPs. Therefore, while delineating the protein-NPs interaction, it is imperative to define the consequences of nanomaterial's introduction and derive data for the formulation of better therapeutic interventions. This review briefly discusses varied types of NPs, their potential applications and interactions with peptides and proteins.
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Nanopartículas , Nanopartículas/química , Peptídeos , ProteínasRESUMO
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.
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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.
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Anti-Infecciosos , Croton , Anti-Infecciosos/farmacologia , Núcleo Caudado , Medicina Tradicional , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Plantas ComestíveisRESUMO
Molecular docking is a process through which small molecules are docked into the macromolecular structures for scoring its complementary values at the binding sites. It is a vibrant research area with dynamic utility in structure-based drug-designing, lead optimization, biochemical pathway and for drug designing being the most attractive tools. Two pillars for a successful docking experiment are correct pose and affinity prediction. Each program has its own advantages and drawbacks with respect to their docking accuracy, ranking accuracy and time consumption so a general conclusion cannot be drawn. Moreover, users don't always consider sufficient diversity in their test sets which results in certain programs to outperform others. In this review, the prime focus has been laid on the challenges of docking and troubleshooters in existing programs, underlying algorithmic background of docking, preferences regarding the use of docking programs for best results illustrated with examples, comparison of performance for existing tools and algorithms, state of art in docking, recent trends of diseases and current drug industries, evidence from clinical trials and post-marketing surveillance are discussed. These aspects of the molecular drug designing paradigm are quite controversial and challenging and this review would be an asset to the bioinformatics and drug designing communities.
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Descoberta de Drogas/métodos , Bibliotecas de Moléculas Pequenas/química , Algoritmos , Desenho de Fármacos , Humanos , Simulação de Acoplamento Molecular , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/farmacologia , Relação Estrutura-AtividadeRESUMO
The largest family of drug targets in clinical trials constitute of GPCRs (G-protein coupled receptors) which accounts for about 34% of FDA (Food and Drug Administration) approved drugs acting on 108 unique GPCRs. Factors such as readily identifiable conserved motif in structures, 127 orphan GPCRs despite various de-orphaning techniques, directed functional antibodies for validation as drug targets, etc. has widened their therapeutic windows. The availability of 44 crystal structures of unique receptors, unexplored non-olfactory GPCRs (encoded by 50% of the human genome) and 205 ligand receptor complexes now present a strong foundation for structure-based drug discovery and design. The growing impact of polypharmacology for complex diseases like schizophrenia, cancer etc. warrants the need for novel targets and considering the undiscriminating and selectivity of GPCRs, they can fulfill this purpose. Again, natural genetic variations within the human genome sometimes delude the therapeutic expectations of some drugs, resulting in medication response differences and ADRs (adverse drug reactions). Around ~30 billion US dollars are dumped annually for poor accounting of ADRs in the US alone. To curb such undesirable reactions, the knowledge of established and currently in clinical trials GPCRs families can offer huge understanding towards the drug designing prospects including "off-target" effects reducing economical resource and time. The druggability of GPCR protein families and critical roles played by them in complex diseases are explained. Class A, class B1, class C and class F are generally established family and GPCRs in phase I (19%), phase II(29%), phase III(52%) studies are also reviewed. From the phase I studies, frizzled receptors accounted for the highest in trial targets, neuropeptides in phase II and melanocortin in phase III studies. Also, the bioapplications for nanoparticles along with future prospects for both nanomedicine and GPCR drug industry are discussed. Further, the use of computational techniques and methods employed for different target validations are also reviewed along with their future potential for the GPCR based drug discovery.
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Descoberta de Drogas/métodos , Preparações Farmacêuticas/química , Receptores Acoplados a Proteínas G/química , Ensaios Clínicos como Assunto , Cristalografia por Raios X , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Humanos , Terapia de Alvo Molecular , Mutação , Preparações Farmacêuticas/síntese química , Conformação Proteica , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/genética , Relação Estrutura-AtividadeRESUMO
The essential oil extracted from fruit of Micromelum integrrimum were evaluated through gas chromatography and gas chromatography-mass spectroscopy. 52 compounds were identified from the fruit oil representing 99.98% of the oil. The major components of the total fruit oil are monoterpene hydrocarbons (72.23%), oxygenated monoterpenes (14.78%) and sesquiterpene (11.54%) which were predominated by terpinolene (32.21%), α-pinene (17.24%), ß-pinene (17.24%), and camphene (4.05%). Moreover, other components that present in 1.45% were aromatic compounds, fatty acid, etc. The essential oil exhibited broad spectrum antimicrobial activity which is concentration dependent and 100 µL of the fruit oil showed the inhibition zones ranging from 7-16 mm. Fruit oil exhibited strong inhibition activity compared to standard anti-bacterial drug neomycin B (22 mm) against Bacillus subtilis MTCC 441 and Bacillus spizizenii ATCC 6633. This is the first hand report on the chemical profiles and promising anti-microbial activity of Micromelum integrrimum fruit essential oil towards Basillus Sp.
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Antibacterianos/isolamento & purificação , Frutas/química , Óleos Voláteis/química , Rutaceae/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Monoterpenos/análise , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Óleos Voláteis/farmacologia , Sesquiterpenos/análise , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologiaRESUMO
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.
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Antineoplásicos/farmacologia , Óleos Voláteis/química , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Simulação de Acoplamento Molecular , Estrutura Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-AtividadeRESUMO
Star fishes (Asteroidea) are rich in polar steroids with diverse structural characteristics. The structural modifications of star fish steroids occur at 3ß, 4ß, 5α, 6α (or ß), 7α (or ß), 8, 15α (or ß) and 16ß positions of the steroidal nucleus and in the side chain. Widely found polar steroids in starfishes include polyhydroxysteroids, steroidal sulfates, glycosides, steroid oligoglycosides etc. Bioactivity of these steroids is less studied; only a few reports like antibacterial, cytotoxic activity etc. are available. In continuation of our search for bioactive molecules from natural sources, we undertook in silico screening of steroids from star fishes against Bcl-2 and CDK-4/Cyclin D1 - two important targets of progression and proliferation of cancer cells. We have screened 182 natural steroids from star fishes occurring in different parts of the world and their 282 soft-derivatives by in silico methods. Their physico-chemical properties, drug-likeliness, binding potential with the selected targets, ADMET (absorption, distribution, metabolism, toxicity) were predicted. Further, the results were compared with those of existing steroidal and non steroidal drugs and inhibitors of Bcl-2 and CDK-4/Cyclin D1. The results are promising and unveil that some of these steroids can be potent leads for cancer treatments.