A review on structure-function mechanism and signaling pathway of serine/threonine protein PIM kinases as a therapeutic target.

The proviral integration for the Moloney murine leukemia virus (PIM) kinases, belonging to serine/threonine kinase family, have been found to be overexpressed in various types of cancers, such as prostate, breast, colon, endometrial, gastric, and pancreatic cancer. The three isoforms PIM kinases i.e., PIM1, PIM2, and PIM3 share a high degree of sequence and structural similarity and phosphorylate substrates controlling tumorigenic phenotypes like proliferation and cell survival. Targeting short-lived PIM kinases presents an intriguing strategy as in vivo knock-down studies result in non-lethal phenotypes, indicating that clinical inhibition of PIM might have fewer adverse effects. The ATP binding site (hinge region) possesses distinctive attributes, which led to the development of novel small molecule scaffolds that target either one or all three PIM isoforms. Machine learning and structure-based approaches have been at the forefront of developing novel and effective chemical therapeutics against PIM in preclinical and clinical settings, and none have yet received approval for cancer treatment. The stability of PIM isoforms is maintained by PIM kinase activity, which leads to resistance against PIM inhibitors and chemotherapy; thus, to overcome such effects, PIM proteolysis targeting chimeras (PROTACs) are now being developed that specifically degrade PIM proteins. In this review, we recapitulate an overview of the oncogenic functions of PIM kinases, their structure, function, and crucial signaling network in different types of cancer, and the potential of pharmacological small-molecule inhibitors. Further, our comprehensive review also provides valuable insights for developing novel antitumor drugs that specifically target PIM kinases in the future. In conclusion, we provide insights into the benefits of degrading PIM kinases as opposed to blocking their catalytic activity to address the oncogenic potential of PIM kinases.

Nanosynthesis, phycochemical constituents, and pharmacological properties of cyanobacterium Oscillatoria sp.

The Oscillatoria sp., a blue-green alga or cyanobacterium, consists of about 305 species distributed globally. Cyanobacteria are prokaryotes possessing several secondary metabolites that have industrial and biomedical applications. Particularly, the published reviews on Oscillatoria sp. have not recorded any pharmacology, or possible details, while the detailed chemical structures of the alga are reported in the literature. Hence, this study considers pertinent pharmacological activities of the plethora of bioactive components of Oscillatoria sp. Furthermore, the metallic nanoparticles produced with Oscillatoria sp. were documented for plausible antibacterial, antifungal, antioxidant, anticancer, and cytotoxic effects against several cultured human cell lines. The antimicrobial activities of solvent extracts of Oscillatoria sp. and the biotic activities of its derivatives, pyridine, acridine, fatty acids, and triazine were structurally described in detail. To understand the connotations with research gaps and provide some pertinent prospective suggestions for further research on cyanobacteria as potent sources of pharmaceutical utilities, attempts were documented. The compounds of Oscillatoria sp. are a potent source of secondary metabolites that inhibit the cancer cell lines, in vitro. It could be expected that by holistic exploitation, the natural Oscillatoria products, as the source of chemical varieties and comparatively more potent inhibitors, would be explored against pharmacological activities with the integument of SARs.

Prospective Phycocompounds for Developing Therapeutics for Urinary Tract Infection.

Antibiotic resistance of bacteria is causing clinical and public health concerns that are challenging to treat. Infections are becoming more common in the present era, and patients admitted to hospitals often have drug-resistant bacteria that can spread nosocomial infections. Urinary tract infections (UTIs) are among the most common infectious diseases affecting all age groups. There has been an increase in the proportion of bacteria that are resistant to multiple drugs. Herein is a comprehensive update on UTI-associated diseases: cystitis, urethritis, acute urethral syndrome, pyelonephritis, and recurrent UTIs. Further emphasis on the global statistical incidence and recent advancement of the role of natural products in treating notorious infections are described. This updated compendium will inspire the development of novel phycocompounds as the prospective antibacterial candidate.

Investigation of in vitro antimicrobial, antioxidant and antiproliferative activities of Nostoc calcicola biosynthesized gold nanoparticles.

The cyanobacteria are the promising candidate for synthesizing gold nanoparticles (AuNPs), due to their ability to accumulate heavy metals from the cellular environment and additionally contain varied bioactive compounds as reducing and stabilizing agents. This study describes the N2-fixing cyanobacterium Nostoc calcicola-mediated bioreduction of AuNPs and the inherent antimicrobial, antioxidant, and antiproliferative activities in vitro. Biosynthesized Nc-AuNPs were characterized by spectral characterization techniques. The formation of AuNPs was physically confirmed by the colour change from pale green to dark violet. The UV-Vis analysis, further, proved the reduction in Nc-AuNPs with the cyanobacterium and showed a spectral peak at 527 nm. FESEM-EDX images suggested the surface morphology of the NPs as spherical, cuboidal, and size between 20 and 140 nm. The antimicrobial studies of Nc-AuNPs were carried out by agar-well diffusion method and MIC values against five pathogenic bacterial and two fungal strains were noted. The AuNPs exhibited potential antimicrobial activity against h-pathogenic bacteria with inhibitory zones ranging at 11-18 mm; against fungi ranging at 13-17 mm. Significant antioxidant potentialities were explored by a DPPH assay with an IC50 value of 55.97 µg/ mL. Furthermore, in the anticancer efficacy assay, the Nc-AuNPs inhibited cellular proliferation in human breast adenocarcinoma and cervical cancer cell lines at IC50 concentration, 37.3 µg/ml, and 44.5 µg/ml, respectively. Conclusively, N. calcicola would be an excellent source for synthesizing stable colloidal AuNPs that had significant credibility as phycological (algal) nanomedicines as novel prodrugs with multiple bioactivities.

Insight to biotechnological utility of phycochemicals from cyanobacterium Anabaena sp.: An overview.

Cyanobacteria (blue-green algae) are well-known for the ability to excrete extra-cellular products, as a variety of cyanochemicals (phycocompounds) of curio with several extensive therapeutic applications. Among these phycocompound, the cyanotoxins from certain water-bloom forming taxa are toxic to biota, including crocodiles. Failure of current non-renewable source compounds in producing sustainable and non-toxic therapeutics led the urgency of discovering products from natural sources. Particularly, compounds of the filamentous N2-fixing Anabaena sp. have effective antibacterial, antifungal, antioxidant, and anticancer properties. Today, such newer compounds are the potential targets for the possible novel chemical scaffolds, suitable for mainstream-drug development cascades. Bioactive compounds of Anabaena sp. such as, anatoxins, hassallidins and phycobiliproteins have proven their inherent antibacterial, antifungal, and antineoplastic activities, respectively. Herein, the available details of the biomass production and the inherent phyco-constituents namely, alkaloids, lipids, phenols, peptides, proteins, polysaccharides, terpenoids and cyanotoxins are considered, along with geographical distributions and morphological characteristics of the cyanobacterium. The acquisitions of cyanochemicals in recent years have newly addressed several pharmaceutical aliments, and the understanding of the associated molecular interactions of phycochemicals have been considered, for plausible use in drug developments in future.

Role of phytocompounds as the potential anti-viral agent: an overview.

Viral diseases are the most notorious infective agent(s) causing morbidity and mortality in every nook and corner for ages; viruses are active in host cells, and specific anti-virus medicines' developments remain uncanny. In this century of the biological era, human viruses act predominantly as versatile spreaders. The infection of the present COVID-19 virus is up in the air; blithely, the integument of medicinal chemistry approaches, particularly bioactive derived phytocompounds could be helpful to control those human viruses, recognized in the last 100 years. Indeed, natural products are being used for various therapeutic purposes. The major bioactive phytocompounds are chemically containing coumarin, thiosulfonate, steroid, polysaccharide, tannin, lignin, proanthocyanidin, terpene, quinone, saponin, flavonoid, alkaloid, and polyphenol, that are documented for inhibitory action against several viral infections. Mostly, about 20-30% of plants from tropical or temperate regions are known to have some antiviral activity. This comprehensive analysis of bioactive-derived phytocompounds would represent a significant impact and might be helpful for antiviral research and the current state of viral treatments.

Recent progression on phytochemicals and pharmacological properties of the filamentous cyanobacterium Lyngbya sp.

The distribution and phytochemistry of the non-nitrogen fixing, filamentous cyanobacterium (blue-green alga) Lyngbya sp., and the inherent antimicrobial and anticancer activities of its phycochemicals as well as of the biosynthesized nanoparticles as their pharmaceutical potencies are considered. Several phycocompounds of curio, apramide, apratoxin, benderamide, cocosamides, deoxymajusculamide, flavonoids, lagunamides, lipids, proteins, amino acids, lyngbyabellin, lyngbyastatin, majusculamide, peptides, etc. were isolated from Lyngbya sp., which had a lot of potential pharmaceutical activities; those compounds had antibacterial, antiviral, antifungal, anticancer, antioxidant, anti-inflammatory, ultraviolet protectant, and other activities. Particularly, several Lyngbya phycocompounds had potent antimicrobial potencies, seen through in vitro controlling of several frequently encountered multidrug-resistant (MDR) clinically belligerent strains of pathogenic bacteria isolated from clinical samples. The aqueous extracts of Lyngbya sp. were used for the synthesis of silver and copper oxide nanoparticles, which were used in pharmacological trials too. The nanoparticles biosynthesized with Lyngbya sp. had several uses such as biofuel, agro-based applications, in cosmetics, and industrial uses as biopolymers, and being potent antimicrobial and anticancer agents and in drug-delivery too, as medical applications. It could be concluded that the Lyngbya phycochemicals and the biosynthesized nanoparticles have future uses as antimicrobial namely as bacterial and fungal and anti-cancer agents, with promising medical and industrial uses.

Recent progression of cyanobacteria and their pharmaceutical utility: an update.

Cyanobacteria (blue-green algae) are Gram-negative photosynthetic eubacteria that are found everywhere. This largest group of photosynthetic prokaryotes is rich in structurally novel and biologically active compounds; several of which have been utilized as prospective drugs against cancer and other ailments, as well. Consequently, the integument of nanoparticles-synthetic approaches in cyanobacterial extracts should increase pharmacological activity. Moreover, silver nanoparticles (AgNPs) are small materials with diameters below 100 nm that are classified into different classes based on their forms, sizes, and characteristics. Indeed, the biosynthesized AgNPs are generated with a variety of organisms, algae, plants, bacteria, and a few others, for the medicinal purposes, as the bioactive compounds of curio and some proteins from cyanobacteria have the potentiality in the treatment of a wide range of infectious diseases. The critical focus of this review is on the antimicrobial, antioxidant, and anticancer properties of cyanobacteria. This would be useful in the pharmaceutical industries in the future drug development cascades.Communicated by Ramaswamy H. Sarma.

Role of hormone receptors and HER2 as prospective molecular markers for breast cancer: An update.

This review provides an updated account on the current methods, principles and mechanism of action of therapies for the detection of molecular markers of therapeutic importance in the prognosis of breast cancer progression and recurrence, which includes estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor2 (HER2). Indeed, hormone-receptors namely, ER, PR, proto-oncogene HER2 are the basic molecular markers that are recognized and established prognostic factors and predictors of response, for therapeutic practice. These markers can be detected by using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), which are established, faster and cost effective detection methods. These molecular markers along with clinicopathological prognostic parameters give the best prediction of the prognosis of cancer recurrence and progress. Finally, hormone receptors and HER2 as molecular markers are of prime therapeutic importance and have the capability to take part in future drug development techniques.

Biomedical Applications of Biosynthesized Gold Nanoparticles from Cyanobacteria: an Overview.

Recently there had been a great interest in biologically synthesized nanoparticles (NPs) as potential therapeutic agents. The shortcomings of conventional non-biological synthesis methods such as generation of toxic byproducts, energy consumptions, and involved cost have shifted the attention towards green syntheses of NPs. Among noble metal NPs, gold nanoparticles (AuNPs) are the most extensively used ones, owing to the unique physicochemical properties. AuNPs have potential therapeutic applications, as those are synthesized with biomolecules as reducing and stabilizing agent(s). The green method of AuNP synthesis is simple, eco-friendly, non-toxic, and cost-effective with the use of renewable energy sources. Among all taxa, cyanobacteria have attracted considerable attention as nano-biofactories, due to cellular uptake of heavy metals from the environment. The cellular bioactive pigments, enzymes, and polysaccharides acted as reducing and coating agents during the process of biosynthesis. However, cyanobacteria-mediated AuNPs have potential biomedical applications, namely, targeted drug delivery, cancer treatment, gene therapy, antimicrobial agent, biosensors, and imaging.

Molecular dynamics simulation, synthesis and topoisomerase inhibitory actions of vanillin derivatives: a systematic computational structural integument.

A series of 4-hydroxy-3-methoxy benzaldehyde (vanillin) derivatives (3a-3r) was designed for the principle of Schiff base condensation with several individual sulfanilamide analogues. The inhibitory potencies of the designed compounds were evaluated through molecular docking simulation studies against the targets, breast cancer-topo isomerase-IIα and estrogen receptor-α; and the top scoring poses with higher binding energy were selected to assess the mode of binding and stability of each complex through molecular dynamics simulations. Compounds that remained stable in the active sites of the both target receptors through a number of strong H-bonds and hydrophobic contacts were selected. Based on the computational results, these selected compounds, 3b, 3e and 3f were synthesized and were followed up for structural elucidation attempts, by FT/ATR, 1H NMR and 13C NMR. From the experimental in vitro studies on 3b, 3e and 3f, the following remarkable activities against breast cancer cell line were done; IC50 values of 3b, 3e and 3f were noted, 6.7, 4.3 and 11 ng/mL, respectively. These newly synthesized compounds may be used as novel inhibitors of nuclear receptors with potential therapeutic applications in control of cancer.Communicated by Ramaswamy H. Sarma.

The recent development of thymol derivative as a promising pharmacological scaffold.

Thymol (a phenol ring bearing active phytoconstituent) is a privileged scaffold, which is diversified in natural sources. This scaffold acts as an obligatory template for scheming and arriving at designing some newer drug-molecules with potential biological activities. In the pharmacological perspective, the promising active sites of the scaffold are the positions C-1, C-4, and C-6 of thymol that would be accountable for developing potent drug candidates. This review aims to explore the various synthetic routes and the structural-activity relationship of thymol scaffold with suitable active pharmacophore sites.

Molecules with versatile biological activities bearing antipyrinyl nucleus as pharmacophore.

Antipyrine (1,2-dihydro-1,5-dimethyl-2-phenylpyrazole-3-one) in a structural frame consists of a five membered lactam pyrazolone heterocyclic ring as a pharmacophore moiety. It is evident from literature that the molecules having nitrogen bearing heterocyclic nuclei clearly exhibit several biological actions. Commercially available pyrazolone derivatives as drugs, analgin and metamizol are an established chemical class of analgesics. Recent trends of synthetic routes and several biological actions of antipyrine analogues are considered in this review. Indeed, the synthesized derivatives possess antipyrine moiety having versatile biological properties, antimicrobial, antitubercular, anthelmintic, antioxidant, analgesic, anti-inflammatory, cytotoxic and antiviral activities.

Norharmane as a potential chemical entity for development of anticancer drugs.

Cancer is a leading cause of death generally, and to overcome this problem the introduction of a new drug developing is a continuous endeavour. An alkaloid, norharmane and its derivatives, which have anticancer activities, widely distributed in several living and synthetic chemical sources. Herewith, the suggested mechanisms of organic reactions and synthetic approaches of norharmane available so far were considered. Active sites of norharmane nucleus positions, C-1, C-3, and N-9, were used for developing new molecules and based on structure activity relationship (SAR), those have been seen with anticancer activities. This review summarizes on chemistry of synthetic strategies of norharmane derivatives, which may provide a framework to design a novel anticancer drug, in future.