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BACKGROUND: Nanophytosomes represent an effective choice for topical drug delivery systems thanks to their small size, general non-toxicity, ease of functionalization and high surface to volume ratio. The goal of the current study was to investigate the potential benefits of using Hypericum perforatum extract nanogel as a means of improving skin penetration and prolonging skin deposition in dermatitis similar to psoriasis. METHOD: Nanophytosomes (NPs) were developed, optimised and thoroughly characterised. The optimised NPs were then placed in a Carbopol gel base matrix and tested ex-vivo (skin penetration and dermatokinetic) and in-vivo (antipsoriatic activity in an Imiquimod-induced psoriatic rat model). RESULTS: The optimised NPs had a spherical form and entrapment efficiency of 69.68% with a nanosized and zeta potential of 168nm and -10.37mV, respectively. XRD spectra and transmission electron microscopy tests confirmed the plant botanical encapsulation in the NPs. Following 60 days of storage at 40 ± 2°C/75 ± 5% RH, the optimised formula remained relatively stable. As compared to extract gel, nano-gel showed a much-improved ex vivo permeability profile and considerable drug deposition in the viable epidermal-dermal layers. When developed nano-gel was applied topically to a rat model of psoriasis, it demonstrated distinct in vivo anti-psoriatic efficacy in terms of drug activity and reduction of epidermal thickness in comparison to other formulations and the control. ELISA and histopathologic studies also demonstrated that nano-organogel had improved skin integrity and downregulated inflammatory markers (IL-17, IL-6, IFN-γ and MCP-1). CONCLUSION: Findings suggest that a developed plant botanicals-based nanogel has a potential for the treatment of psoriasis-like dermatitis with better skin retention and effectiveness.
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Nanoemulsions are gaining interest in a variety of products as a means of integrating easily degradable bioactive compounds, preserving them from oxidation, and increasing their bioavailability. However, preparing stable emulsion compositions with the desired characteristics is a difficult task. The aim of this study was to encapsulate the Tinospora cordifolia aqueous extract (TCAE) into a water in oil (W/O) nanoemulsion and identify its critical process and formulation variables, like oil (27-29.4 mL), the surfactant concentration (0.6-3 mL), and sonication amplitude (40% to 100%), using response surface methodology (RSM). The responses of this formulation were studied with an analysis of the particle size (PS), free fatty acids (FFAs), and encapsulation efficiency (EE). In between, we have studied a fishbone diagram that was used to measure risk and preliminary research. The optimized condition for the formation of a stable nanoemulsion using quality by design was surfactant (2.43 mL), oil concentration (27.61 mL), and sonication amplitude (88.6%), providing a PS of 171.62 nm, FFA content of 0.86 meq/kg oil and viscosity of 0.597 Pa.s for the blank sample compared to the enriched TCAE nanoemulsion with a PS of 243.60 nm, FFA content of 0.27 meq/kg oil and viscosity of 0.22 Pa.s. The EE increases with increasing concentrations of TCAE, from 56.88% to 85.45%. The RSM response demonstrated that both composition variables had a considerable impact on the properties of the W/O nanoemulsion. Furthermore, after the storage time, the enriched TCAE nanoemulsion showed better stability over the blank nanoemulsion, specially the FFAs, and the blank increased from 0.142 to 1.22 meq/kg oil, while TCAE showed 0.266 to 0.82 meq/kg.
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Emulsiones , Tamaño de la Partícula , Extractos Vegetales , Tinospora , Agua , Emulsiones/química , Extractos Vegetales/química , Tinospora/química , Agua/química , Sonicación , Nanopartículas/química , Aceites/química , Tensoactivos/químicaRESUMEN
This study was designed to assess both the quality and cost aspects of various branded and generic formulations of angiotensin receptor blockers, specifically Irbesartan, Losartan Potassium, Olmesartan Medoxomil, Telmisartan, and Valsartan. The collected samples underwent distinct quality evaluations using the methods outlined in different global Pharmacopoeias (British Pharmacopoeia/European Pharmacopoeia, Indian Pharmacopoeia and United States Pharmacopoeia). These drugs were characterized using Fourier-Transform Infrared Spectroscopy and Nuclear Magnetic Resonance techniques, while their quality and concentration were analysed using High Performance Liquid Chromatography. The release profile of the drugs was examined through dissolution testing. Additionally, a cost comparison analysis was carried out by determining the prevailing market prices of the drugs. The evaluated branded and generic angiotensin receptor blockers were found to meet the established standards for impurities, active drug content, and dissolution as set by these Pharmacopoeias, indicating their optimal quality. Notably, the generic drugs exhibited significantly lower costs compared to their branded counterparts. This study confirms that the quality of generic angiotensin receptor blockers is equivalent to that of their branded counterparts. Consequently, these findings support the practicality of utilizing generic drugs as a more economically sustainable and cost-effective approach to managing diseases, especially those of chronic nature.
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INTRODUCTION: The widespread importance of the synthesis and modification of anticancer agents has given rise to many numbers of medicinal chemistry programs. In this regard, triazine derivatives have attracted attention due to their remarkable activity against a wide range of cancer cells. This evaluation covers work reports to define the anticancer activity, the most active synthesized compound for the target, the SAR and, when described, the probable MOA besides similarly considered to deliver complete and target-pointed data for the development of types of anti-tumour medicines of triazine derivatives. Triazine scaffold for the development of anticancer analogues. Triazine can also relate to numerous beneficial targets, and their analogues have auspicious in vitro and in vivo anti-tumour activity. Fused molecules can improve efficacy, and drug resistance and diminish side effects, and numerous hybrid molecules are beneath diverse stages of clinical trials, so hybrid derivatives of triazine may offer valuable therapeutic involvement for the dealing of tumours. OBJECTIVE: The objective of the recent review was to summarize the recent reports on triazine as well as its analogues with respect to its anticancer therapeutic potential. CONCLUSION: The content of the review would be helpful to update the researchers working towards the synthesis and designing of new molecules for the treatment of various types of cancer disease with the recent molecules that have been produced from the triazine scaffold. Triazine scaffolds based on 1,3,5-triazine considerably boost molecular diversity levels and enable covering chemical space in key medicinal chemistry fields.
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The purpose of immunization is the effective cellular and humoral immune response against antigens. Several studies on novel vaccine delivery approaches such as micro-particles, liposomes & nanoparticles, etc. against infectious diseases have been investigated so far. In contrast to the conventional approaches in vaccine development, a virosomes-based vaccine represents the next generation in the field of immunization because of its balance between efficacy and tolerability by virtue of its mechanism of immune instigation. The versatility of virosomes as a vaccine adjuvant, and delivery vehicle of molecules of different nature, such as peptides, nucleic acids, and proteins, as well as provide an insight into the prospect of drug targeting using virosomes. This article focuses on the basics of virosomes, structure, composition formulation and development, advantages, interplay with the immune system, current clinical status, different patents highlighting the applications of virosomes and their status, recent advances, and research associated with virosomes, the efficacy, safety, and tolerability of virosomes based vaccines and the future prospective.
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Propolis is rich in natural bioactive compounds, and considering its importance for many skin therapies, emulgel was prepared. This study examines how a propolis extract (PE) and Passiflora edulis seed (PS) oil emulgel affect rat deep skin wound healing. Based on preset criteria of maximum drug content and optimum drug permeation through the stratum corneum along with drug retention in the skin layers, an optimized emulgel formula based on Box-Behnken factorial design was prepared and used for subsequent in vitro and in vivo evaluations. In vivo wound-healing activities of emulgel and control treatments were investigated in a rat model. The optimized emulgel formula exhibited superior healing activity compared with plain PE suspension-treated rats on day 14 of wounding. Histopathological investigations of hematoxylin and eosin and Masson's Trichrome-stained skin sections supported this effect. Emulgel promotes cutaneous wound healing through a variety of mechanisms, including anti-inflammatory through modulation of cytokines tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 production, and promotion of collagen fiber formation, all of which contribute to tissue remodeling. Furthermore, when compared with propolis suspension, emulgel showed significant antioxidant and anti-inflammatory effects. Emulgel significantly increased the skin's hydroxyproline level, antioxidant potential, wound contraction, increased penetration, and localized propolis deposition across the skin. Incorporation of PS oil into the emulgel accelerates the tissue regeneration process. The findings suggest that 5% propolis emulgel could be used as an alternative to treat wounds.
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Passiflora , Própolis , Cicatrización de Heridas , Animales , Ratas , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Colágeno/metabolismo , Colágeno/farmacología , Citocinas/metabolismo , Citocinas/farmacología , Eosina Amarillenta-(YS)/farmacología , Hematoxilina/farmacología , Hidroxiprolina/farmacología , Interleucina-6/farmacología , Passiflora/química , Passiflora/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Aceites de Plantas/farmacología , Aceites de Plantas/uso terapéutico , Própolis/farmacología , Própolis/uso terapéutico , Factor de Necrosis Tumoral alfa/farmacología , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Temperature-induced, rapid changes in the viscosity and reproducible 3-D structure formation makes thermos-sensitive hydrogels an ideal delivery system to act as a cell scaffold or a drug reservoir. Moreover, the hydrogels' minimum invasiveness, high biocompatibility, and facile elimination from the body have gathered a lot of attention from researchers. This review article attempts to present a complete picture of the exhaustive arena, including the synthesis, mechanism, and biomedical applications of thermosensitive hydrogels. A special section on intellectual property and marketed products tries to shed some light on the commercial potential of thermosensitive hydrogels.
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Even though various treatment methods are available for cancer, the death curve is not reducing. The diagnosis of cancer at the fourth stage and drug resistance are the leading reasons for treatment failure and lower survival rates. In this review article, we summarize the possible pitfalls during cancer treatment in general, which mainly include multidrug resistance, and propose a hypothesis for colorectal cancer specifically. We also evaluate multidrug resistance in cancer in general and colorectal cancer in particular and hypothesize a concept based on combination therapy with 5-fluorouracil, curcumin, and lipids for the possible management of colorectal cancer. In addition, a hypothetical approach, combining a synthetic agent and a natural chemotherapeutic agent, to treating colorectal cancer is also discussed. This hypothesis could improve the management of colorectal cancer.
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P-glycoprotein (P-gp) is a major factor in the multidrug resistance phenotype in cancer cells. P-gp is a protein that regulates the ATP-dependent efflux of a wide range of anticancer medicines and confers resistance. Due to its wide specificity, several attempts have been made to block the action of P-gp to restore the efficacy of anticancer drugs. The major goal has been to create molecules that either compete with anticancer medicines for transport or function as a direct P-gp inhibitor. Despite significant in vitro success, there are presently no drugs available in the clinic that can "block" P-gp-mediated resistance. Toxicity, unfavourable pharmacological interactions, and a variety of pharmacokinetic difficulties might all be the reason for the failure. On the other hand, P-gp has a significant effect in the body. It protects the vital organs from the entry of foreign bodies and other toxic chemicals. Hence, the inhibitors of P-gp should not hinder its action in the normal cells. To develop an effective inhibitor of P-gp, thorough background knowledge is needed in this field. The main aim of this review article was to set forth the merits and demerits of the action of P-gp on cancer cells as well as on normal cells. The influence of P-gp on cancer drug delivery and the contribution of P-gp to activating drug resistance were also mentioned.
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In this study, silver nanoparticles (AgNPs) are synthesized through a green approach by employing Rosa indica L. petal (RE) extracts as reducing and stabilizing agents, which are extracted using three different solvents: ethanol (Et), acetone (Ac), and water (Aq). The phase formation of the AgNPs is confirmed using X-ray diffraction (XRD). Morphological analysis is performed using a field-emission scanning electron microscope (FESEM), which reveals that the AgNPs are spherical in shape. The size is estimated using ImageJ software, which is found to be ~12, 18, and 770 nm for RE-Ac-Ag, RE-Et-Ag, and RE-Aq-Ag, respectively. The phytochemicals of Rosa indica L. petals involved in the formation of the AgNPs are studied using Fourier transform infrared spectroscopy (FTIR). Finally, these materials are studied for their antibacterial, antidiabetic, antioxidant, and hemolytic activity, as well as cell toxicity properties. The materials, RE-Ac-Ag and RE-Et-Ag, are found to be more effective than RE-Aq-Ag in inhibiting E. coli (Gram-negative bacteria) and S. aureus (Gram-positive bacteria). Hemolytic studies reveal that all of the samples show concentration-dependent activity up to 50 µg/mL. RE-Ac-Ag and RE-Et-Ag exhibit nonhemolytic behavior, whereas RE-Aq-Ag remains nonhemolytic until 100 µg/mL. The antidiabetic ability of the AgNPs is evaluated using α-amylase inhibition assay (DNSA assay) and α-glucosidase inhibition assay. The results are found to be effective, with IC50 values of α-amylase and α-glycosidase being 50, 50, and 75 µg/mL for RE-Et-Ag, RE-Ac-Ag, and RE-Aq-Ag, respectively. DPPH assay shows that the AgNPs inhibited the antioxidants well, with IC50 values of 40 µg/mL for RE-Et-Ag and RE-Ac-Ag and 60 µg/mL for RE-Aq-Ag. The toxicity study reveals that the AgNPs show size- and concentration-dependent behavior. Overall, it is realized from the findings that RE-Ac-Ag, RE-Et-Ag, and RE-Aq-Ag show size-dependent antibacterial, antidiabetic, and toxicity properties.
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Pralsetinib (PRL) is a selective Rearranged during Transfection (RET) inhibitor, developed by Blueprint Medicines Corporation for the treatment of RET fusion non-small-cell lung cancer (NSCLC), papillary thyroid cancer (PTC), and medullary thyroid carcinoma (MTC). RET is a known proto-oncogene found in NSCLC, PTC, and MTC. PRL was recently granted accelerated USFDA approval with the brand name GAVRETO™ on 4 September 2020 to treat metastatic RET fusion-positive NSCLC and was updated on 1 December 2020 with the addition of advanced and metastatic RET-altered MTC and PTC in the USA. On 19 November 2021, the European Commission granted conditional marketing authorization to PRL for use as a single agent in adult patients with RET fusion-positive advanced NSCLC. They were not previously treated with an RET inhibitor. This review article summarizes the milestones in the development of PRL, chemistry, chemical (synthesis) research and development, characterization and identification of PRL-resistant RET mutants, the structural basis of resistance to PRL, mechanism of action, pharmacokinetics, pharmacodynamic, adverse effects, and regulatory status, including ongoing clinical trial of PRL and other potential drug candidates, leading to this first approval of PRL for the treatment of various solid tumors (RET fusion NSCLC, MTC, and PTC).
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Neuroendocrino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-ret/genética , Proteínas Proto-Oncogénicas c-ret/uso terapéutico , Pirazoles , Piridinas , Pirimidinas , Neoplasias de la Tiroides , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Pegfilgrastim-apgf (nyvepria) was currently approved by FDA for the treatment of febrile neutropenia associated with non-myeloid malignancies receiving myelosuppressive anticancer drugs. It was developed by Pfizer, USA. It is a PEGylated leukocyte growth-stimulating factor indicated to reduce the incidence of febrile neutropenia in patients receiving anticancer drugs. Nyvepria is biosimilar to pegfilgrastim, approved by FDA on June 10, 2020. It is the fourth FDA-approved drug for the treatment of infection exhibiting febrile neutropenia. This review abridges the indicators in the development of nyvepria foremost to approval for the treatment of febrile neutropenia (FN), a biosimilar regulatory framework, and current updates on the clinical trials (CTs).
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Biosimilares Farmacéuticos , Neutropenia Febril Inducida por Quimioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biosimilares Farmacéuticos/efectos adversos , Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Neutropenia Febril Inducida por Quimioterapia/etiología , Filgrastim/efectos adversos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Polietilenglicoles/efectos adversos , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Belumosudil (BLM) is a ROCK inhibitor that has been firstly developed by Surface Logix, later acquired by Kadmon Pharmaceuticals for the treatment of chronic graft-versus-host disease (cGVHD), Psoriasis Vulgaris (PV), idiopathic pulmonary fibrosis (IPF), hepatic impairment (HI), diffuse cutaneous systemic sclerosis (dcSSc). BLM received a breakthrough therapy designation and priority review from the FDA, which reviewed the NDA under the real-time oncology review (RTOR) pilot programme and approved it six weeks ahead of the PDUFA deadline of August 30, 2021. On July 16th, 2021, The USFDA authorized BLM under the brand name REZUROCKTM for the treatment of cGVHD in adults and pediatric patients aged ≥ 12 years after the failure of at least two prior lines of systemic therapy. It has been granted orphan drug status by the FDA on August 9, 2020, for the treatment of systemic sclerosis. The European Union (EU) granted Quality Regulatory Clinical Ireland Limited, Ireland, orphan drug status for BLM (KD025) for the treatment of cGVHD on October 17, 2019. BLM is under regulatory assessment by Therapeutic Good Administration (TGA) Australia, Health Canada, MHRA (UK), and The Swiss Agency for Therapeutic Products (Swissmedic), Switzerland for cGVHD. A clinical trial is ongoing in the United States for cutaneous systemic sclerosis. This review article summarizes the milestones in the development of BLM chemistry, Chemical synthesis and development, mechanism of action, pharmacokinetics (PK), pharmacodynamics (PD), adverse effects, regulatory status, and ongoing clinical trials (CT) of BLM.
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Enfermedad Injerto contra Huésped , Esclerodermia Sistémica , Acetamidas/efectos adversos , Adulto , Niño , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Humanos , Estados Unidos/epidemiología , United States Food and Drug AdministrationRESUMEN
Psoriasis is an autoimmune skin disorder that is characterised by chronic inflammation and erythematous scaly patches. It has a significant impact on the patient's quality of life and can cause psychological stress. There are several aspects that cause psoriasis, for instance, environmental issues, immune disorders, bacterial infections, and genetic issues. Plentiful therapeutic means or treatments are accessible, but not any of them can completely and effectively cure psoriasis without hindering patient compliance. Hence, it becomes challenging to discover a new drug moiety or any drug delivery method to cure psoriasis. Conventional treatment of psoriasis involves anti-inflammatory agents, immune suppressants, phototherapy, and biological treatment, which were given in different forms such as topical, oral, or systemic formulations, but these all were unsuccessful to accomplish complete reduction of psoriasis as well as causing adverse side effects. In terms of dose frequency, doses, efficacy, and side effects, nanotechnology-based new formulations are the most promising prospects for addressing the challenges and limits associated with present psoriasis formulations. Hence, our major goal of this review is to present various advanced nanotechnological approaches for the effective topical treatment of psoriasis. In short, nano-formulations continue to be formed as very promising modalities in the treatment of psoriasis as they suggest improved penetration, targeted delivery, increased safety, and efficacy.
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Psoriasis , Calidad de Vida , Administración Tópica , Humanos , Inmunosupresores/efectos adversos , Nanotecnología , Psoriasis/tratamiento farmacológicoRESUMEN
Inebilizumab-cdon (Uplizna™) was currently approved by the United States Food and Drug Administration (USFDA) for the treatment of NMOSD (neuromyelitis optica spectrum disorder). It was developed by Viela Bio (Nasdaq: VIE) USA. Inebilizumab-cdon (formerly MEDI-551) is a humanized antibody, which induces CD19 + B cell depletion by increasing antibody-dependent cell cytotoxicity (ADCC) and cell phagocytosis (ADCP) of effector cells. Various clinical trials exhibit its safe and effective pharmacokinetic and pharmacodynamic profile. In June 2019, Viela Bio submitted Biologics License Application (BLA) to the FDA based on the findings obtained from the N-Momentum trial. This article summarizes the milestones in the development of Inebilizumab-cdon leading to this approval for the treatment of advanced NMOSD.
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Neuromielitis Óptica , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Acuaporina 4/uso terapéutico , Humanos , Neuromielitis Óptica/tratamiento farmacológico , Estados Unidos , United States Food and Drug AdministrationRESUMEN
INTRODUCTION: Breast cancer (BC) is one of the most frequent malignancies and the most common reasons for impermanence in women. The backbone of therapy for BC is principally chemotherapy, but its non-specific nature to differentiate between normal cells and cancer cells and severe side effects are the main barriers in its use. So, there is an intense requirement to enlarge more efficacious, more specific and safer anti-BC agents. OBJECTIVE: Isatin (IST) is an endogenous molecule that is a principal class of heterocyclic compounds and exhibits a wide range of therapeutic activities which can be used as a starting material for the synthesis of several drug molecules. Many kinds of literature were reported previously on different pharmacological activities of IST derivatives and particularly on anticancer activity but this review mainly focuses on anti-BC activities of IST derivatives through MCF-7, MDA MB 231, MDA-MB 435 and MDA-MB 468 cell lines. Herein we mentioned; a total of 33 IST derivatives (compound 24- 56) which show good anti-BC activity. IST-derived compounds are also available in the market and are used for various cancer types like sunitinib for renal cell carcinoma (RCC) and Nintedanib for the cryptogenic fibrosing alveolitis treatment, but when evaluated for BC, they did not prove to be much successful. CONCLUSION: This review mainly highlights anti-BC activities of various IST analogues using MCF-7, MDA MB 231, MDA-MB 435 and MDA-MB 468 cell lines, displaying the potent compound of the series and structure-activity relationships of compounds with molecular docking also. So, this study mainly shows the importance of IST as a major source for drug design and development of newer anti-BC drugs.
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Antineoplásicos , Neoplasias de la Mama , Isatina , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Isatina/farmacología , Células MCF-7 , Simulación del Acoplamiento Molecular , Estructura MolecularRESUMEN
Teprotumumab (TPT) is a type I insulin-like growth factor receptor inhibitor, marketed as Tepezza; recently USFDA approved it for the treatment of thyroid eye disease (thyroid-associated ophthalmopathy (TAO), Graves ophthalmopathy/orbitopathy) in the USA. It is a monoclonal antibody although it was initially developed in collaboration with Genmab and Roche for the treatment of the tumour, but later it was investigated by River Vision Development Corporation and Horizon Therapeutics for its ophthalmic use. The drug has been designated as an orphan drug, breakthrough designation and fast-track designation. This review summarizes the milestones in the research and development including ongoing, clinical trial of TPT till now, foremost to this primary approval for thyroid-associated ophthalmopathy (TAO).
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Oftalmopatía de Graves , Anticuerpos Monoclonales Humanizados , Oftalmopatía de Graves/tratamiento farmacológico , Humanos , Receptor IGF Tipo 1 , Estados Unidos , United States Food and Drug AdministrationRESUMEN
BACKGROUND: Isatin (IST) is a crucial pharmacologically active compound, chemically known as indole- 1H-2,3-dione. Development of different IST based analogues acquired significant awareness because of its pronounced therapeutic importance such as analgesic, anticancer, anti-inflammatory, antitubercular, antimicrobial, antifungal, antiviral (effective against SARS coronavirus 3C protease) and many other activities, and represents an important class of heterocyclic compounds that can be used as a precursor for the synthesis of many useful drugs. OBJECTIVE: Previously, many articles were reported on IST synthesis and its different pharmacological activities but herein, we mentioned 59 different synthesis schemes of several IST derivatives/hybrids derived from the substitution of the nitrogen, aromatic ring, the second and third position of IST along with most potent molecule among each of synthesized libraries with their structural activity relationship (SAR). Using these standardized approaches, several biologically important compounds were developed like sunitinib, nintedanib, indirubin, etc and several studies have been carried out nowadays to develop newer compounds having fewer side effects and also overcome the problem of resistance. CONCLUSION: This report critically reviews the different strategies for the designs and synthesis of several IST based compounds having different biological activities with SAR, which can favour further investigation and modification for the development of new and more potent entities.
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Antiinfecciosos , Isatina , Analgésicos , Antiinflamatorios , Antituberculosos , Isatina/farmacologíaRESUMEN
BACKGROUND: This review elaborates the updated synthetic and pharmacological approaches of a known group of dihydropyrimidinones/thiones from the multi-component reaction like Biginelli reaction, which was named Pietro Biginelli in 1891. This review consists of the reaction of an aromatic aldehyde, urea and ethyl acetoacetate leading to dihydropyrimidinone/thione. Currently, the scientific movement to develop economically viable green methods using compounds that are reusable, non-volatile, easily obtained, etc. Objective: This review covers the recent synthesis and pharmacological advancement of dihydropyrimidinones/ thiones moiety, along with covering the structure-activity relationship of the most potent compounds, which may prove to become better, more efficacious and safer agents. Thus, this review may help the researchers in drug designing and development of new Dihydropyrimidinones entities. CONCLUSION: This review focuses on the wide application of dihydropyrimidinone/thione review reports the design, synthesis and pharmacological activities of nitrogen-sulphur containing dihydropyrimidinone moiety by using multi-component reaction. Dihydropyrimidinones (DHPM) pharmacophore is an important heterocyclic ring in medicinal chemistry. It is derived from multi-component reactions, "Biginelli reaction" and plays a critical role as anticancer, antioxidant, antimicrobial, anti-inflammatory, anti-HIV-1, antimalarial, anti-inflammatory, antihypertensive and anti-tubercular agents. Exhaustive research has led to its vast biological profile, with a wide range of therapeutic application.
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Antiinfecciosos , Pirimidinonas , Antibacterianos , Pirimidinonas/farmacología , Relación Estructura-Actividad , TionasRESUMEN
Dengue fever is prevalent in subtopic regions, producing mortality and morbidity worldwide, which have been of major concern to different governments and World Health Organization. The search of new anti-dengue agents from phytochemicals was assumed to be highly emergent in past. The phytochemicals have been used in wide distribution of vector ailments such as malaria. The demand of the phytochemicals is based on the medicines which are mostly considered to be safer, less harmful than synthetic drugs and nontoxic. This review mentions majorly about the phytochemicals potentially inhibiting dengue fever around the world. The phytochemicals have been isolated from different species, have potential for the treatment of dengue. Different crude extracts and essential oils obtained from different species showed a broad activity against different phytochemicals. The current studies showed that natural products represent a rich source of medicines toward the dengue fever. Furthermore, ethnobotanical surveys and laboratory investigation established identified natural plants species in the development of drug discovery to control the dengue fever.