Open Medicinal Chemistry Journal最新文献

Background: Sulindac belongs to the chemically diverse family of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that effectively prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA), an amide analog of sulindac sulfide, shows insignificant COX-related activity and toxicity while enhancing anticancer activity in vitro and demonstrating in vivo xenograft activity.

Objective: Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities.

Method: A series of sulindac amine analogs were designed and synthesized and then further modified in a "libraries from libraries" approach to produce amide, sulfonamide and N,N-disubstituted sulindac amine sub-libraries. All analogs were screened against three cancer cell lines (prostate, colon and breast).

Results: Several active compounds were identified viain vitro cancer cell line screening with the most potent compound (26) in the nanomolar range.

Conclusion: Compound 26 and analogs showing the most potent inhibitory activity may be considered for further design and optimization efforts as anticancer hit scaffolds.

Background: A novel drug delivery system for treating acute epileptic condition.

Objective: To develop an intranasal mucoadhesive formulation of Lamotrigine (LTG) loaded insitu gel, for the treatment of epilepsy to avoid possible side effects and first pass metabolism associated with conventional treatment.

Methods: Lamotrigine was loaded into different polymeric solutions of gellan and xanthan gum.

Results: All formulations subjected to various evaluation studies were within their acceptable limits. The pH of formulation ranges between 5.8 ±.001 to 6.8 ±.005 indicating that no mucosal irritation is expected as pH was in acceptable range. Invitro drug release from the mucoadhesive insitu gel formulations showed immediate drug release pattern with a maximum drug release of 97.02 ±0.54% for optimized G5 formulation within 20min. Exvivo permeation studies of optimized formulation G5 and control formulation was estimated. Exvivo permeation studies of G5 insitu formulation done for a period of 12 h resulted in slow, sustained release and greater permeability significance(P <0.05) through nasal mucosa when compared to control. Histopathological studies showed that G5 formulation was safer for nasal administration without any irritation. The stability studies indicated that gels were stable over 45 days in refrigerated condition (4±2ºC).

Conclusion: The intranasal insitu gelling system is a promising novel drug delivery system for an antiepileptic drug lamotrigine which could enhance nasal residence time with increased viscosity and mucoadhesive character and provided better release profile of drug for treating acute epileptic conditions.

Background: Quantitative Structure Activity Relationship (QSAR) is a difficult computational chemistry approach for beginner scientists and a time consuming one for even more experienced researchers.

Method and materials: Ezqsar which is introduced here addresses both the issues. It considers important steps to have a reliable QSAR model. Besides calculation of descriptors using CDK library, highly correlated descriptors are removed, a provided data set is divided to train and test sets, descriptors are selected by a statistical method, statistical parameter for the model are presented and applicability domain is investigated.

Results: Finally, the model can be applied to predict the activities for an extra set of molecules for a purpose of either lead optimization or virtual screening. The performance is demonstrated by an example.

Conclusion: The R package, ezqsar, is freely available via https://github.com/shamsaraj/ezqsar, and it runs on Linux and MS-Windows.

Background: Selegiline is used to treat Parkinsonian patients. Other indications of its use have recently been discovered.

Objective: Scouting special and beneficial side effects of selegiline treatment.

Method: Two-year old male Wistar rats were daily treated with 0.25 mg/kg of selegiline s.c. (subcutaneous injection). The rats were sacrificed following a four-weeks' treatment.

Results: Mass of testes, number of sperms, progressive motility of sperms, and their viability definitely increased.

Conclusion: Selegiline can successfully be used to stop/counterbalance certain symptoms of aging.

Introduction: Ebola Virus Disease (EVD) is caused by Ebola virus, which is often accompanied by fatal hemorrhagic fever upon infection in humans. This virus has caused the majority of deaths in human. There are no proper vaccinations and medications available for EVD. It is pivoting the attraction of scientist to develop the potent vaccination or novel lead to inhibit Ebola virus.

Methods & materials: In the present study, we developed 3D-QSAR and the pharmacophoric model from the previous reported potent compounds for the Ebola virus.

Results & discussion: Results & Discussion: The pharmacophoric model AAAP.116 was generated with better survival value and selectivity. Moreover, the 3D-QSAR model also showed the best r2 value 0.99 using PLS factor. Thereby, we found the higher F value, which demonstrated the statistical significance of both the models. Furthermore, homological modeling and molecular docking study were performed to analyze the affinity of the potent lead. This showed the best binding energy and bond formation with targeted protein.

Conclusion: Finally, all the results of this study concluded that 3D-QSAR and Pharmacophore models may be helpful to search potent lead for EVD treatment in future.

Intoroduction: Prodrug approach deals with chemical biotransformation or enzymatic conversion or involves inactive or less active bio-reversible derivatives of active drug molecules. They have to pass through enzymatic or chemical biotransformation before eliciting their pharmacological action.

Methods & materials: The two different pharmacophores combine to give synergistic activity or may help in targeting the active drug to its target. Prodrug super seeds the problems of prodrug designing, for example solubility enhancement, bioavailability enhancement, chemical stability improvement, presystemic metabolism, site specific delivery, toxicity masking, improving patient acceptance, or eradicating undesirable adverse effects.

Results: As an outcome the search for a prodrug or mutual prodrug with reduced toxicity has continued during recent years. This present review emphasizes the common help to revamp physiochemical, pharmaceutical and therapeutic effectiveness of drugs.

Conclusion: This gives the researcher a common platform where they can find prodrugs of commonly used NSAIDs to overcome the gastrointestinal toxicity (irritation, ulcergenocity and bleeding).

Introduction: The 1,3-dipolar cycloaddition reactions of nitrile oxides formed in situ (in the presence of NCS and Et₃N) from the oximes of (purin-9-yl)acetaldehyde or (coumarinyloxy)acetaldehyde with allyloxycoumarins or 9-allylpurines, respectively resulted in 3,5-disubstituted isoxazolines. The similar reactions of propargyloxycoumarins or 9-propargylpurines led to 3,5-disubstituted isoxazoles by treatment with PIDA and catalytic amount of TFA.

Methods: The new compounds were tested in vitro as antioxidant agents and inhibitors of soybean lipoxygenase LO, AChE and MAO-B.

Results: The majority of the compounds showed significant hydroxyl radical scavenging activity. Compounds 4k and 4n presented LO inhibitory activity.

Conclusion: Compound 13e presents an antioxidant significant profile combining anti-LO, anti-AChE and anti-MAO-B activities.

Introduction: Graft copolymerization is one of the most promising technique uses to modify the properties of naturally available polymers with a minimum loss in their native characteristics.

Methods and materials: Graft copolymerization is a very significant technique to add hybrid properties in backbone of polymers. The grafting generally initiated through the formation of free radical centers on the polymer backbone as well as monomer.

Results: Grafted polysaccharides have various applications in different important scientific areas such as drug delivery, pharmaceutical field, plastic industry, waste water treatment, tannery effluent treatment, textile industry, agriculture area, etc. all of this fascinated us to summarize the major research articles over the last two decades outlining different methods of grafting, surface modification, graft copolymerization of synthetic and natural polymers.

Conclusion: Various redox initiator systems viz. Ceric ammonium nitrate, per sulfate, Irradiation, FAS-H₂O₂etc. is also explored for grafting of vinyl through conventional and non-conventional techniques.

Introduction: In efforts to develop new antitubercular (anti-TB) compounds, herein we describe cytotoxic evaluation of 15 newly synthesized pyrrolyl pyrazoline carbaldehydes.

Method & materials: Surflex-Docking method was used to study binding modes of the compounds at the active site of the enzyme enoyl ACP reductase from Mycobacterium tuberculosis (M. tuberculosis), which plays an important role in FAS-II biosynthetic pathway of M. tuberculosis and also it is an important target for designing novel anti-TB agents.

Results: Among the synthesized compounds, compounds 4g and 4i showed H-bonding interactions with MET98, TYR158 and co-factor NAD⁺, all of which fitted well within the binding pocket of InhA. Also, these compounds have shown the same type of interaction as that of 4TZK ligand. The compounds were further evaluated for preliminary anti-TB activities against M. tuberculosis H37Rv strain.

Conclusion: Some compounds were also screened for their mammalian cell toxicity using human lung cancer cell-line (A549) that was found to be nontoxic.

Introduction: New benzopyrone derivatives such as Schiff's like compounds, acetohydrazides or substituted with oxadiazole or pyrazole heterocycles were synthesized from parent acid hydrazide compound 3.

Methods and materials: Structures of the synthesized compounds were elucidated using IR, NMR and mass spectroscopy. All the synthesized derivatives were selected by National Cancer Institute (NCI), Bethesda, and evaluated for their in vitro anticancer activity in the full NCI 60 cell lines panel assay.

Results and conclusion: Schiffs like compounds 4a, b and c were found to have good growth inhibition % against numerous cell lines that belong mainly to leukemia, non-small cell lung, CNS and breast Cancer subpanels.