Pyrazoles as Anti-inflammatory and Analgesic Agents: In-vivo and In-silico Studies.

BACKGROUND: Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant, antiviral, and anticancer activities. There are well-known marketed drugs having pyrazole moiety as celecoxib, and lonazolac as COX-II inhibitors. AIMS: We aim to synthesize better anti-inflammatory than existing ones. Thiophene is also known for its analgesic and anti-inflammatory action. Thus, the fusion of both gives better anti-inflammatory agents. In the present studies, derivatives from two series of pyrazole were prepared by reacting substituted chalcone (3a-3f) derivatives prepared from 2-acetyl thiophene. They substituted aromatic aldehydes with phenyl hydrazine to form (5a-5f) and with 2, 4-dinitro phenyl hydrazine giving compounds (6a-6f) separately. METHODS: Purified and characterized pyrazoles have been analyzed for in-vivo analgesic and anti-inflammatory activities by using standard methods. Compounds 5e, 5f, and 6d were proved to be potent analgesics and series (5a-5f) was found to have anti-inflammatory action, which was further validated using docking and ADME studies. RESULTS: The ADME profile of synthesized compounds was found to be satisfactory. CONCLUSION: The synthesized compounds can serve as lead for further drug designing.

Unlocking the Pharmacological Potential of Benzimidazole Derivatives: A Pathway to Drug Development.

Heterocyclic molecules have fascinated a massive interest in medicinal chemistry. They are heterocyclic compounds that have gained significance due to their diverse variety of pharmacological activities. Benzimidazole is a heterocyclic compound consisting of benzene and imidazole rings. The ease of synthesis and the structural versatility of benzimidazole make it a promising scaffold for drug development. Many biological actions of benzimidazole derivatives have been well documented, including antibacterial, antiviral, anticancer, anti-inflammatory, antitubercular, and anthelmintic properties. The mechanism of action of benzimidazole derivatives varies with their chemical structure and target enzyme. This review has explored numerous methods for producing benzimidazole derivatives as well as a broad range of pharmacological activities. SAR investigations are also discussed in this review as they provide crucial details regarding the essential structural qualities that benzimidazole derivatives must have in order to be biologically active, which could aid in the rational design of new drug candidates. Benzimidazole scaffold is an exclusive structure in drug design and discovery. Many new pharmaceutical drugs containing benzimidazole are anticipated to be available within the next ten years as a result of the extensive therapeutic applications of benzimidazole and its derivatives. This review inspired many researchers to develop more biologically active compounds bearing benzimidazole, expanding the scope of finding a remedy for other diseases. From this study, we concluded that 2-substituted benzimidazole was considered more extensively by researchers.

Prodrug Rewards in Medicinal Chemistry: An Advance and Challenges Approach for Drug Designing.

This article emphasizes the importance of prodrugs and their diverse spectrum of effects in the field of developing novel drugs for a variety of biological applications. Prodrugs are chemicals that are supplied inactively, but then go through enzymatic and chemical transformation in vivo to release the active parent medication that can have the desired pharmacological effect. By adding an inactive chemical moiety, prodrugs are improved in a number of ways that contribute to their potency and durability. For the purpose of illustrating the usefulness of the prodrug approach, this review covers examples of prodrugs that have been made available or are now undergoing human trials. Additionally, it included lists of the most common functional groups, carrier linkers, and reactive chemicals that can be used to create prodrugs. The current study also provides a brief introduction, several chemical methods and modifications for creating prodrugs and mutual prodrugs, as well as an explanation of recent advancements and difficulties in the field of prodrug design. The primary chemical carriers employed in the creation of prodrugs, such as esters, amides, imides, NH-acidic carriers, amines, alcohols, carbonyl, carboxylic, and azo-linkages, are also discussed. This review also discusses glycosidic and triglyceride mutually activated prodrugs, which aim to deliver the drugs after bioconversion at the intended site of action. The article also discusses the extensive chemistry and wide variety of applications of recently approved prodrugs, such as antibacterial, anti-inflammatory, cardiovascular, antiplatelet, antihypertensive, atherosclerotic, antiviral, etc. In order to illustrate the prodrug and mutual drug concept's various applications and highlight its many triumphs in overcoming the formulation and delivery of problematic pharmaceuticals, this work represents a thorough guide that includes the synthetic moiety for the reader.

Pyrazole based Furanone Hybrids as Novel Antimalarial: A Combined Experimental, Pharmacological and Computational Study.

BACKGROUND: Malaria parasite strains are resistant to the therapeutic effect of prophylactics medicines presently available. This resistance now poses a significant challenge to researchers to beat malaria parasitic infections. Strategies such as investigating newer hybrid chemical entities and specified drug targets may help us spot new efficient derivatives that bind to the parasites in a more specific manner and inhibit their growth. OBJECTIVE: To scientifically perform the experimental, pharmacological, and computational studies of pyrazole-based furanone hybrids as novel antimalarial agents. METHODS: A series of new furanone-based pyrazole derivatives were synthesized and investigated as potential antimalarial agents by performing in vitro antimalarial activity. To get further optimization, these synthesized derivatives were virtually screened based on ADME-T filters, and molecular docking studies were also accomplished on the crystal structures of Plasmodium falciparum lactate dehydrogenase (PfLDH). Furthermore, the in-silico prediction was supported by performing an LDH assay. RESULTS: The docking data suggested that the designed hybrid of furanone-pyrazole may act as PfLDH inhibitors. It was found that the results of experimental in vitro antimalarial activity and in silico analysis correlate well to each other to a good extent. The compounds (7d), (7g), and (8e) were found to be the most potent derivatives with IC50 values of 1.968, 1.983, and 2.069 µg/ml, respectively. CONCLUSION: From the results, it may be concluded that compounds that are active in low doses might be adopted as a lead compound for the development of more active antimalarial agents. The synthesized compounds (7d), (7g), and (8e) exhibited good antimalarial activity with PfLDH inhibition. The best compounds can be explored further in the future for designing the potent inhibitors of PfLDH as new potent antimalarial agents.