Functional Studies of Plant Latex as a Rich Source of Bioactive Compounds: Focus on Proteins and Alkaloids

Latex, a sticky emulsion produced by specialized cells called laticifers, is a crucial part of a plant’s defense system against herbivory and pathogens. It consists of a broad spectrum of active compounds, which are beneficial not only for plants, but for human health as well, enough to mention the use of morphine or codeine from poppy latex. Here, we reviewed latex’s general role in plant physiology and the significance of particular compounds (alkaloids and proteins) to its defense system with the example of Chelidonium majus L. from the poppy family. We further attempt to present latex chemicals used so far in medicine and then focus on functional studies of proteins and other compounds with potential pharmacological activities using modern techniques such as CRISPR/Cas9 gene editing. Despite the centuries-old tradition of using latex-bearing plants in therapies, there are still a lot of promising molecules waiting to be explored.

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Structural and Functional Investigation and Pharmacological Mechanism of Trichosanthin, a Type 1 Ribosome-Inactivating Protein

Toxins ◽

10.3390/toxins10080335 ◽

2018 ◽

Vol 10 (8) ◽

pp. 335 ◽

Cited By ~ 1

Author(s):

Wei-Wei Shi ◽

Kam-Bo Wong ◽

Pang-Chui Shaw

Keyword(s):

Ribosomal Rna ◽

Ribosome Inactivating Protein ◽

Pharmacological Activities ◽

Pharmacological Mechanism ◽

Functional Studies ◽

P Protein ◽

Ribosomal Stalk ◽

Functional Investigation ◽

Ribosomal P

Trichosanthin (TCS) is an RNA N-glycosidase that depurinates adenine-4324 in the conserved α-sarcin/ricin loop (α-SRL) of rat 28 S ribosomal RNA (rRNA). TCS has only one chain, and is classified as type 1 ribosome-inactivating protein (RIP). Our structural studies revealed that TCS consists of two domains, with five conserved catalytic residues Tyr70, Tyr111, Glu160, Arg163 and Phe192 at the active cleft formed between them. We also found that the structural requirements of TCS to interact with the ribosomal stalk protein P2 C-terminal tail. The structural analyses suggest TCS attacks ribosomes by first binding to the C-terminal domain of ribosomal P protein. TCS exhibits a broad spectrum of biological and pharmacological activities including anti-tumor, anti-virus, and immune regulatory activities. This review summarizes an updated knowledge in the structural and functional studies and the mechanism of its multiple pharmacological effects.

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Steroidal pyrazolines as a promising scaffold in drug discovery

Future Medicinal Chemistry ◽

10.4155/fmc-2019-0325 ◽

2020 ◽

Vol 12 (10) ◽

pp. 949-959

Author(s):

Ranju Bansal ◽

Ranjit Singh

Keyword(s):

Drug Discovery ◽

Broad Spectrum ◽

Chemical Reactivity ◽

Biological Activities ◽

Antimicrobial Activities ◽

Review Article ◽

Pharmacological Activities ◽

Neuroprotective Effects ◽

Wide Range

Steroidal pyrazolines constitute an interesting and promising scaffold for drug discovery as they display diverse chemical reactivity and a wide range of biological activities. Literature reports indicate potent anticancer potential of steroidal pyrazolines along with broad-spectrum antimicrobial activities. Strong neuroprotective effects with steroids possessing pyrazoline moiety have also been observed. Among all the therapeutically active steroidal pyrazolines, D-ring-substituted derivatives are highly potent and the least toxic. The current and futuristic research approaches in this area are focused towards the exploration of this promising scaffold to develop molecules with widespread pharmacological activities. This review article mainly covers the synthetic and pharmacological aspects of steroidal pyrazolines, which will assist the medicinal chemists working in this area in their scientific endeavors.

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Gene editing in tomatoes

Emerging Topics in Life Sciences ◽

10.1042/etls20170056 ◽

2017 ◽

Vol 1 (2) ◽

pp. 183-191 ◽

Cited By ~ 2

Author(s):

Joyce Van Eck

Keyword(s):

Gene Editing ◽

Crop Improvement ◽

Site Directed Mutagenesis ◽

Dna Uptake ◽

Food Crop ◽

Transcription Activator ◽

Base Editing ◽

Crop Models ◽

Functional Studies ◽

Tomato Transformation

Tomato is an effective model plant species because it possesses the qualities necessary for genetic and functional studies, but is also a food crop making what is learned more translatable for crop improvement when compared with other non-food crop models. The availability of genome sequences for many genotypes and amenability to transformation methodologies (Agrobacterium-mediated, direct DNA uptake via protoplasts, biolistics) make tomato the perfect platform to study the application of gene-editing technologies. This review includes information related to tomato transformation methodology, one of the necessary requirements for gene editing, along with the status of site-directed mutagenesis by TALENs (transcription activator-like effector nucleases) and CRISPR/Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated Proteins). In addition to the reports on proof-of-concept experiments to demonstrate the feasibility of gene editing in tomato, there are many reports that show the power of these technologies for modification of traits, such as fruit characteristics (ripening, size, and parthenocarpy), pathogen susceptibility, architecture (plant and inflorescence), and metabolic engineering. Also highlighted in this review are reports on the application of a recent CRISPR technology called base editing that allows the modification of one base pair in a gene sequence and a strategy that takes advantage of a geminivirus replicon for delivery of DNA repair template.

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Discovery of Anticancer Agents from 2-Pyrazoline-Based Compounds

Current Medicinal Chemistry ◽

10.2174/0929867327666200306120151 ◽

2020 ◽

Vol 27 ◽

Cited By ~ 1

Author(s):

Qing-Shan Li ◽

Bang-Nian Shen ◽

Zhen Zhang ◽

Ban-Feng Ruan ◽

Shuying Luo

Keyword(s):

Broad Spectrum ◽

Anticancer Agents ◽

Present Review ◽

Pyrazole Derivatives ◽

Anticancer Activities ◽

Structural Units ◽

Pharmacological Activities ◽

The Relationship

: As nitrogen-containing five-membered heterocyclic structural units, the substituted pyrazole derivatives have broad spectrum of pharmacological activities, especially 4,5-dihydro-1H-pyrazoles that also commonly known as 2-pyrazolines. Since 2010, considerable studies have been found that the 2-pyrazoline derivatives possess potent anticancer activities. In present review, it covers the pyrazoline derivatives reported by literatures from 2010 till date (2010-2019). This review aims to establish the relationship between the anticancer activities variation and different substituents introduced into 2-pyrazoline core, which could provide important pharmacophore clues for the discovery of new anticancer agents that containing 2-pyrazoline scaffold.

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Aryltetralin-type lignan of Podophyllum: a comprehensive review

The Natural Products Journal ◽

10.2174/2210315511666210210160903 ◽

2021 ◽

Vol 11 ◽

Author(s):

Dharmendra Kumar ◽

Mogana Rajagopal ◽

Gabriel Akyirem Akowuah ◽

Yong-Xin Lee ◽

Chua Wei Chong ◽

...

Keyword(s):

Combination Therapy ◽

Chemical Synthesis ◽

Chemical Modification ◽

Broad Spectrum ◽

Anticancer Agent ◽

Review Article ◽

Pharmacological Activities ◽

Comprehensive Review ◽

Podophyllotoxin Derivatives

: Podophyllotoxin is a nonalkaloidtoxin aryltetralin lactone lignan, occurring naturally and extracted from the rhizomes and roots of Podophyllum species. Podophyllotoxin and its derivatives have shown to possess a broad spectrum of pharmacological activities, mainly antineoplastic and antiviral properties. Podophyllotoxin is served as a potential anticancer agent and also the precursor for the chemical synthesis of some clinically important anticancer agents.The chemical modification and pharmacological investigation of podophyllotoxin derivatives have become a concern nowadays. Research interest has been stimulated in the innovation of podophyllotoxin derivatives as the semi-synthetic anticancer agent, especially etoposide and teniposide. Podophyllotoxin and its derivatives are available in several formulations and also found to be effective in combination therapy. This review article aims to provide an overview of the role of podophyllotoxin, its mechanism of action, pharmacological activities, pharmacokinetics, available formulations, and its effects in combination therapy. This article also reviewed the biosynthesis, structure and modifications of podophyllotoxin and its derivatives as an anticancer agent.

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New insights into the construction of wild-type Saba pig-derived Escherichia coli irp2 gene deletion strains

3 Biotech ◽

10.1007/s13205-021-02951-0 ◽

2021 ◽

Vol 11 (9) ◽

Author(s):

Bo Zhang ◽

Hongdan Wang ◽

Weiwei Zhao ◽

Chunlan Shan ◽

Chaoying Liu ◽

...

Keyword(s):

Iron Uptake ◽

Gene Editing ◽

Gene Deletion ◽

Growth Characteristics ◽

Wild Type ◽

Knock Out ◽

E Coli ◽

Functional Studies ◽

Key Points ◽

Type Strains

AbstractTo construct wild-type E. coli irp2 gene deletion strains, CRISPR/Cas9 gene editing technology was used, and the difficulty and key points of gene editing of wild-type strains were analyzed. Based on the resistance of the CRISPR/Cas9 system expression vector, 4 strains of 41 E. coli strains isolated from Saba pigs were selected as the target strains for the deletion of the irp2 gene, which were sensitive to both ampicillin and kanamycin. Then, CRISPR/Cas9 technology was combined with homologous recombination technology to construct recombinant vectors containing Cas9, sgRNA and donor sequences to knock out the irp2 gene. Finally, the absence of the irp2 gene in E. coli was further verified by iron uptake assays, iron carrier production assays and growth curve measurements. The results showed that three of the selected strains showed single base mutations and deletions (Δirp2-1, Δirp2-2 and Δirp2-3). The deletion of the irp2 gene reduced the ability of E. coli to take up iron ions and produce iron carriers, but not affect the growth characteristics of E. coli. It is shown that the CRISPR/Cas9 knock-out system constructed in this study can successfully knock out the irp2 gene of the wild-type E. coli. Our results providing new insights into genome editing in wild-type strains, which enable further functional studies of the irp2 gene in wild-type E. coli.

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A Review: Medicinally Important Nitrogen Sulphur Containing Heterocycles

The Open Medicinal Chemistry Journal ◽

10.2174/1874104502014010049 ◽

2020 ◽

Vol 14 (1) ◽

pp. 49-64

Author(s):

Praveen K. Sharma ◽

Andleeb Amin ◽

M. Kumar

Keyword(s):

Broad Spectrum ◽

Mode Of Action ◽

Mammalian Cells ◽

Heterocyclic Compounds ◽

Structural Features ◽

Present Review ◽

Pharmacological Activities ◽

Sulfur Heterocycles ◽

Biological And Pharmacological Activities

Nitrogen sulphur containing heterocycles have specific properties due to which they can be used as a potential material in a different type of industries such as medicinal/pharmaceutical, paint, packing and textile, required for various chemical, physical operations and their use as products. Especially dyes, paint, agrochemicals, medicine, etc. make them more significant. In present days, Nitrogen-Sulfur heterocycles are repeatedly attracting the interest of chemists due to their exceptional bioactive behavior. The present study is a review of the work carried out by a chemist in the discovery of new, effective, medicinally important heterocyclic compounds. The present review basically focused on nitrogen-sulfur heterocycles of potential therapeutic interest, especially with thiazole, thiazine, pyrimidine, morpholine and piperazine heterosystems, benzothiazines, pyrazole-benzothiazines, morpholine-benzothiazines, piperazine-benzothiazines and pyrimidine-benzothiazoles, mainly due to their unique structural features, which enable them to exhibit a number of biological and pharmacological activities. Due to a novel mode of action, a broad spectrum of activity, lesser toxicity towards mammalian cells, and suitable profiles towards humans have triggered the use of Nitrogen Sulphur containing heterocycles in designing and synthesizing their derivatives with better properties. The overall objective of the review is to discuss the importance of novel biodynamic structurally diverse heterocycles of potential therapeutic interest: pyrimidine, morpholine, piperazine, pyrozole, benothiazoles, pyrimidobenzothiazoles, 4H-1,4-benzothiazines, pyrazolyl-benzothiazines, morpholinyl-benzothiazines and piperazinylbenzothiazines in order to have access to important commercial molecules for the search of better future.

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The new normal of structure/function studies in the era of CRISPR/Cas9

Biochemical Journal ◽

10.1042/bcj20170025 ◽

2018 ◽

Vol 475 (9) ◽

pp. 1635-1642 ◽

Cited By ~ 1

Author(s):

Glennis A. Logsdon ◽

Ben E. Black

Keyword(s):

Gene Expression ◽

Synthetic Biology ◽

Structure Function ◽

Gene Editing ◽

Single Nucleotide ◽

Distant Future ◽

Functional Studies ◽

Biochemical Studies ◽

Endogenous Genes ◽

New Biology

Major advances in gene-editing technologies have enabled the rapid dissection of proteins in complex biological systems, facilitating biological experiments to complement biochemical studies with purified components. In this editorial, we highlight CRISPR/Cas9-based strategies to rapidly manipulate endogenous genes — strategies that have already transformed functional studies of proteins in metazoan systems. We further describe emerging tools using a catalytically dead version of Cas9 (dCas9) that do not cleave DNA, but can alter gene expression and/or local chromatin states, edit single nucleotide bases, and permit the visualization of specific genomic loci. Looking to the not-too-distant future, CRISPR/Cas9-based methodologies promise to lead to discoveries of new biology, opening the door for bold new synthetic biology platforms.

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Targeted mutagenesis using CRISPR-Cas9 in the chelicerate herbivore Tetranychus urticae

10.1101/2019.12.25.888032 ◽

2019 ◽

Author(s):

Wannes Dermauw ◽

Wim Jonckheere ◽

Maria Riga ◽

Ioannis Livadaras ◽

John Vontas ◽

...

Keyword(s):

Genetic Transformation ◽

Tetranychus Urticae ◽

Spider Mite ◽

Gene Editing ◽

Target Gene ◽

Genetic Defect ◽

Targeted Mutagenesis ◽

Desaturase Gene ◽

Functional Studies ◽

Albino Phenotype

AbstractThe use of CRISPR-Cas9 has revolutionized functional genetic work in many organisms, including more and more insect species. However, successful gene editing or genetic transformation has not yet been reported for chelicerates, the second largest group of terrestrial animals. Within this group, some mite and tick species are economically very important for agriculture and human health, and the availability of a gene-editing tool would be a significant advancement for the field. Here, we report on the use of CRISPR-Cas9 to create gene knock-outs in the spider mite Tetranychus urticae. The ovary of virgin adult females was injected with a mix of Cas9 and sgRNAs targeting the phytoene desaturase gene. Natural mutants of this gene have previously shown an easy-to-score albino phenotype. Albino sons of injected virgin females were mated with wild-type females, and two independent transformed lines where created and further characterized. Albinism inherited as a recessive monogenic trait. Sequencing of the complete target-gene of both lines revealed two different lesions at expected locations near the PAM site in the target-gene. Both lines did not genetically complement each other in dedicated crosses, nor when crossed to a reference albino line with a known genetic defect in the same gene. In conclusion, two independent mutagenesis events were induced in the spider mite T. urticae using CRISPR-Cas9, providing an impetus for genetic transformation in chelicerates and paving the way for functional studies using CRISPR-Cas9 in T. urticae.

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