Current Pharmaceutical Design - Volume 28, Issue 41, 2022

Marine microorganisms represent virtually unlimited sources of novel biological compounds and can survive extreme conditions. Cellulases, a group of enzymes that are able to degrade cellulosic materials, are in high demand in various industrial and biotechnological applications, such as in the medical and pharmaceutical industries, food, fuel, agriculture, and single-cell protein, and as probiotics in aquaculture. The cellulosic biopolymer is a renewable resource and is a linearly arranged polysaccharide of glucose, with repeating units of disaccharide connected via β-1,4-glycosidic bonds, which are broken down by cellulase. A great deal of biodiversity resides in the ocean, and marine systems produce a wide range of distinct, new bioactive compounds that remain available but dormant for many years. The marine environment is filled with biomass from known and unknown vertebrates and invertebrate microorganisms, with much potential for use in medicine and biotechnology. Hence, complex polysaccharides derived from marine sources are a rich resource of microorganisms equipped with enzymes for polysaccharides degradation. Marine cellulases’ extracts from the isolates are tested for their functional role in degrading seaweed and modifying wastes to low molecular fragments. They purify and renew environments by eliminating possible feedstocks of pollution. This review aims to examine the various types of marine cellulase producers and assess the ability of these microorganisms to produce these enzymes and their subsequent biotechnological applications.

The marine microenvironment harbors many unique species of organisms that produce a plethora of compounds that help mankind cure a wide range of diseases. The diversity of products from the ocean bed serves as potentially healing materials and inert vehicles carrying the drug of interest to the target site. Several composites still lay undiscovered under the blue canopy, which can provide treatment for untreated diseases that keep haunting the earth periodically. Cancer is one such disease that has been of interest to several eminent scientists worldwide due to the heterogenic complexity involved in the disease's pathophysiology. Due to extensive globalization and environmental changes, cancer has become a lifestyle disease continuously increasing exponentially in the current decade. This ailment requires a definite remedy that treats by causing minimal damage to the body's normal cells. The application of nanotechnology in medicine has opened up new avenues of research in targeted therapeutics due to their highly malleable characteristics. Marine waters contain an immense ionic environment that succors the production of distinct nanomaterials with exceptional character, yielding highly flexible molecules to modify, thus facilitating the engineering of targeted biomolecules. This review provides a short insight into an array of marine biomolecules that can be probed into cancer nanotherapeutics sparing healthy cells.

Recent research has revealed the role of metalloproteinases in a number of severe pathological illnesses, including cardiac, cartilage, neurological, and cancer-related diseases that are fatal to humans. Metalloproteinases are a subclass of endopeptidases that comprise structurally identical enzymes known as Matrix Metalloproteinases (MMPs) that are solely involved in extracellular matrix degradation and play a significant regulatory function in tissue remodeling. Improper regulation and expression of MMPs have been linked to several life-threatening pathological conditions in humans. Hence there is an ever-growing interest in various research communities to identify and report the Matrix Metalloproteinase Inhibitors (MMPIs). In spite of several chemically synthesized MMPIs being available currently, several unpleasant side effects, un-successful clinical trials have made use of synthetic MMPIs as a risky strategy. Several natural product researchers have strongly recommended and reported many natural resources like plants, microorganisms, and animals as greater resources to screen for bioactives that can function as potential natural MMPIs. Marine environment is one of the vast and promising resources that harbor diverse forms of life known to synthesize biologically active compounds. These bioactive compounds from marine organisms have been reported for their unparalleled biological effects and have profound applications in cosmeceutical, nutraceutical, and pharmaceutical research. Several research groups have reported an umpteen number of medicinally unmatched compounds from marine flora and fauna, thus driving researchers to screen marine organisms for natural MMPIs. In this review, our group has reported the potential MMPIs from marine organisms.

Plants are a source of diverse classes of secondary metabolites with anticancer properties. Paclitaxel (Taxol) is an anticancer drug isolated from various Taxus species and is used as a chemotherapeutic agent against various cancers. The biosynthesis of paclitaxel is a complex pathway, making its total chemical synthesis commercially non-viable; hence, alternative novel sources - like plant cell culture and heterologous expression systems, are being investigated to overcome this issue. Advancements in the field of genetic engineering, microbial fermentation engineering, and recombinant techniques have significantly increased the achievable yields of paclitaxel. Indeed, paclitaxel selectively targets microtubules and causes cell cycle arrest in the G2/M phase, inducing a cytotoxic effect in a concentration and time-dependent manner. Innovative drug delivery formulations, like the development of albumin-bound nanoparticles, nano-emulsions, nano-suspensions, liposomes, and polymeric micelles, have been applied to enhance the delivery of paclitaxel to tumor cells. This review focuses on the production, biosynthesis, mechanism of action, and anticancer effects of paclitaxel.

Background: Medicinal chemistry of pyrazolopyrimidine scaffolds substituted with different heterocyclic nuclei has attracted great attention due to their wide range of biological activities that have been reported. Pyrazolopyrimidine scaffold is an important privileged heterocycle nucleus in drug discovery. Methods: All pharmacological activities of pyrazolopyrimidine scaffold have been mentioned, such as anticancer, anti-inflammatory, antihypertensive, antitubercular, antiviral, antibacterial, antifungal, antidiabetic, and anti-obesity agents. In addition, it was used in both osteoporosis and neurological disorders. The difference in potency and bioavailability of pyrazolopyrimidine derivatives refers to the substituent groups that can increase the activity against specific targets and enhance their selectivity. Results: This review provides an overview of different synthetic pathways, structure activity relationships, and preclinical studies of pyrazolopyrimidine scaffolds substituted with a variety of heterocyclic nuclei, as well as it provides a discussion on the significant biological findings of these important scaffolds. In addition, it provides some insights on the different macromolecular targets that pyrazolopyrimidine scaffold can effectively work on, such as; cyclin dependent kinases; CDK2, CDK7, and CDK9, checkpoint kinases; CHK1 and CHK2 and their correlation with the anticancer activity, PI3Kα, transient receptor potential canonical 6, B-Raf kinase, Interleukin- 1 receptor-associated kinase 4, B-cell lymphoma 6, TRKA-C kinase, potent kDa ribosomal protein S6 kinase, colon cancer cell line (CaCo-2), domain receptor kinase (KDR), HepG-2 carcinoma cell, FLT3. The antibacterial activity against B. subtilis and E. coli and antifungal activity against C. albicans, C. tropicalis, A. niger, and A. clavatus are discussed. Conclusion: This review provides an overview of the different pharmacological activities of the pyrazolopyrimidine scaffold and its correlation with chemical structure. Some exciting new developments in pyrazolopyrimidine scaffolds are also presented in this review.

Background: Immune checkpoint inhibitors (ICIs), specifically programmed cell death receptor- 1/ligand 1 (PD-1/L1) inhibitors, have shown potential pharmacological efficacy in several cancers. Nonetheless, data pertinent to their therapeutic efficacy in alveolar soft-part sarcoma (ASPS) are limited. Objective: The retrospective aspects of ICIs (anti-PD1/PD-L1 blockers) to target ASPS are comparatively analyzed for clinical outcomes with other targeted immunotherapy modalities. Methods: We have conducted a systematic review without statistical analysis or comprehensive meta-analysis by collecting the articles published between 1952 and Sep 10th, 2020, by searching the following words: alveolar soft part sarcoma and immunotherapy including immune checkpoint, immune checkpoint inhibitors, and PD-1, PD-L1. We performed a pooled analysis of case reports, conferences, clinical trials, and other research reports pertinent to the efficacy of a PD-1 or PD-L1 antagonist in patients diagnosed with metastatic ASPS. Results: The effective studies include 10 case reports, 2 conference reports, 5 clinical trials, and 2 additional research reports. A total of 110 patients were reported to be enrolled in the pooled analysis; among them, 87 (78.38%) received a PD-1/PD-L1 antagonist. For patients who received anti-PD-1/PD-L1as monotherapy, their clinical response rates (CRR) were 63.22% whereas those who received targeted therapy and immunotherapy had a CRR of 78.95% (15/19). In the patients treated with double immunotherapy, their CRR was 100% (4/4). Tumor mutational burden and mismatch repair status have significant implications for predicting the ASPS prognosis. Conclusion: Alveolar soft-part sarcoma patients with distant metastases can exhibit better clinical outcomes with immunotherapy, particularly toripalimab, atezolizumab, and axitinib combinatorial regimen with pembrolizumab. In addition, this review describes the therapeutic implications to guide personalized medicine depending on the expression patterns of PD-1/PD-L1 during the immunotherapy with ASPS.