Molecular Diversity

<p><em>Molecular Diversity</em> publishes full-length research papers and both full-length and short reviews. Coverage addresses the generation of molecular diversity, application of diversity for screening against alternative targets of all types, analysis of results and their application in various scientific disciplines. Topics include combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design <strong>with applications of artificial intelligence and machine learning (AI/ML)</strong>; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics; automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution; origin of life and recombination, search techniques; landscapes; random chemistry and more. </p> <p><strong>The journal focuses on exploring the structure-function relationship of diverse molecular structures at the interface of chemistry, biology, and informatics, covering pharmacodynamic and pharmacokinetic aspects. In addition, the journal has broadened its scope to cover the structure-function relationship in the context of environmental health effects of chemical exposome. However, the following topics are excluded from the scope: </strong></p> <strong>Chemical analysis and analytical method development </strong> <strong> Materials science research </strong> <strong> Pharmacological studies and Computational biology work without a significant chemistry component </strong> <strong> Research on plant extracts, and/or herbal/polyherbal formulations as components of traditional medicine </strong> <strong> Natural products isolation and structural determination</strong>

List of Papers (Total 212)

Interpretable Quantitative Structure–Activity Relationship (QSAR) for identification of potent antifungal activity agents towards Candida albicans ATCC 2091

Fungal infections are an increasing global health issue. Despite available treatments, fungal resistance reduces medicine effectiveness. This research conducted QSAR analysis on fifty-one 4-aryl-2-hydrazinothiazole derivatives previously evaluated for antifungal activity. The QSAR model was derived from a hybrid method combining genetic algorithms (GA) and multiple linear...

An innovative approach to development of new pyrazolylquinolin-2-one hybrids as dual EGFR and BRAFV600E inhibitors

Novel quinoline-based derivatives 2a–e and 4a–j have been designed and synthesized as potential antiproliferative agents. The designed compounds were screened for their antiproliferative activity against sixty cell lines according to NCI protocol. The promising hybrids 4d–g are screened by MTT assays on three cancer cell lines: leukemia (MOLT-4), lung cancer (HOP-92), and breast...

Structural insights of AKT and its activation mechanism for drug development

AKT1, a serine/threonine kinase, is pivotal in signaling and regulating cell survival, proliferation, and metabolism. This review focuses on the structural insights and the essential features required for its active conformation. AKT belongs to the AGC kinase group and has three isoforms: AKT1, AKT2, and AKT3. AKT has three functional regions: PH domain, kinase domain, and...

Design and synthesis of novel pyrimidine-pyrazole hybrids with dual anticancer and anti-inflammatory effects targeting BRAFV600E and JNK

Two new series of pyrimidinyl ethyl pyrazoles derivatives 13a–f and 14a–f were designed and synthesized to possess both anticancer effect by inhibiting BRAFV600E and anti-inflammatory effect by inhibiting JNK isoforms. The structure of the new compounds was generated from hybridization of two main moieties. The pyrimidinyl moiety from reported BRAFV600E inhibitors, and the...

Synthesis and biological evaluation of rationally designed pyrazoles as insecticidal agents

The current research focused on the synthesis of two series of pyrazole derivatives and evaluation of their insecticidal effectiveness. In the first series, seven pyrazole Schiff bases 3a-g were successfully synthesized with yields (79–95%) by condensing phenylfuran-2-carbaldehyde with substituted pyrazole rings. In the second series, eleven amino acid-pyrazole conjugates 6a–k...

Coumarin derivatives containing the 1,3,4 oxadiazole/thiadiazole moiety discovered as potential anti-tobacco mosaic virus agents

In this paper, a series of oxadiazole/thidiazole containing coumarin derivative derivatives were designed, synthesized and characterized using NMR and HRMS. The evaluation of antiviral activity revealed that some of the synthesized compounds exhibited good in vivo antiviral efficacy against tobacco mosaic virus (TMV). Notably, compounds H6 and Y5 demonstrated exceptional...

Computational screening and molecular dynamics of natural compounds targeting the SH2 domain of STAT3: a multitarget approach using network pharmacology

SH2 (Src Homology 2) domains play a crucial role in phosphotyrosine-mediated signaling and have emerged as promising drug targets, particularly in cancer therapy. STAT3 (Signal Transducer and Activator of Transcription 3), which contains an SH2 domain, plays a pivotal role in cancer progression and immune evasion because it facilitates the dimerization of STAT3, which is...

Identification of STAT3 phosphorylation inhibitors using generative deep learning, virtual screening, molecular dynamics simulations, and biological evaluation for non-small cell lung cancer therapy

The development of phosphorylation-suppressing inhibitors targeting Signal Transducer and Activator of Transcription 3 (STAT3) represents a promising therapeutic strategy for non-small cell lung cancer (NSCLC). In this study, a generative model was developed using transfer learning and virtual screening, leveraging a comprehensive dataset of STAT3 inhibitors to explore the...

In silico screening of phytochemicals against chromatin modifier, SETD7 for remodeling of the immunosuppressive tumor microenvironment in renal cancer

The tumor microenvironment and immune evasion function in a complex cellular network profoundly challenge the clinical outcome of promising therapies. Our recently published study reported that the subset of genes upregulated in ccRCC due to H3K4me1 and DNA demethylation potentially leads to an immunosuppressive environment. Thus, modulating H3K4me1 chromatin modifier SETD7 with...

An overview on pharmaceutical applications of phosphodiesterase enzyme 5 (PDE5) inhibitors

Phosphodiesterase enzyme 5 (PDE5) inhibitors have emerged as one of the leading molecules for the treatment of erectile dysfunction (ED). PDE5 inhibitors are categorized structurally into several classes. PDE5 inhibitors have been a multidisciplinary endeavor that attracts the attention of researchers because of their multiple pharmaceutical applications. Beyond their action on...

Insight on novel sulfamoylphenyl pyrazole derivatives as anticancer carbonic anhydrase inhibitors

As another part continue for our previous study, variable substituted pyrazoles bearing sulfamoylphenyl moiety were synthesized and screened against two cancer related human carbonic anhydrase (hCA) isoforms and acetazolamide (AAZ) used as a reference standard. Some compounds as 4e and 6c manifested a promising inhibitory activity against both isoforms (KI = 0.072, 0.081 and 0...

Design, synthesis, and anti-breast cancer activity evaluation of novel 3-cyanopyridine derivatives as PIM-1 inhibitors

A novel series of cyanopyridines 7a-j were synthesized via a one-pot multicomponent reaction of arylidene 4 with ammonium acetate 5 and respective methylaryl/heterylketones 6a-j in ethanol using vanillin as a natural starting material. Moreover, the regioselective alkylation reaction was studied by the treatment of cyanopyridines 7a-f and 7j with CH3I in the presence of K2CO3 in...

Pyroptosis and chemical classification of pyroptotic agents

Pyroptosis, as a lytic-inflammatory type of programmed cell death, has garnered considerable attention due to its role in cancer chemotherapy and many inflammatory diseases. This review will discuss the biochemical classification of pyroptotic inducers according to their chemical structure, pyroptotic mechanism, and cancer type of these targets. A structure-activity relationship...

Identification of potential NUDT5 inhibitors from marine bacterial natural compounds via molecular dynamics and free energy landscape analysis

NUDIX hydrolase 5 (NUDT5) is an enzyme involved in the hydrolysis of nucleoside diphosphates linked to other moieties, such as ADP-ribose. This cofactor is vital in redox reactions and is essential for the activity of sirtuins and poly(ADP-ribose) polymerases, which are involved in DNA repair and genomic stability. It has been shown that NUDT5 activity can also influence NAD...

One pot multi-component synthesis of novel functionalized pyrazolo furan-2(5H)-one derivatives: in vitro, DFT, molecular docking, and pharmacophore studies, as coronavirus inhibitors

New and facile one-pot approach for the syntheses of 12 derivatives of 3,5-disubstituted furane-2(5H)-one (4a–l) from easily available starting materials. The suitable synthetic procedures for selective synthesis of diverse furane-2(5H)-one derivatives were achieved via multi-component condensation of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1), pyruvic acid and different...

(-)-Epicatechin metabolites as a GPER ligands: a theoretical perspective

Diet habits and nutrition quality significantly impact health and disease. Here is delve into the intricate relationship between diet habits, nutrition quality, and their direct impact on health and homeostasis. Focusing on (-)-Epicatechin, a natural flavanol found in various foods like green tea and cocoa, known for its positive effects on cardiovascular health and diabetes...

Identification of mycobacterial Thymidylate kinase inhibitors: a comprehensive pharmacophore, machine learning, molecular docking, and molecular dynamics simulation studies

Thymidylate kinase (TMK) is a pivotal enzyme in Mycobacterium tuberculosis (Mtb), crucial for phosphorylating thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), thereby playing a critical role in DNA biosynthesis. Dysregulation or inhibition of TMK activity disrupts DNA replication and cell division, making it an attractive target for anti-tuberculosis drug...

Benzimidazole scaffold as a potent anticancer agent with different mechanisms of action (2016–2023)

Benzimidazole scaffolds have potent anticancer activity due to their structure similarity to nucleoside. In addition, benzimidazoles could function as hydrogen donors or acceptors and bind to different drug targets that participate in cancer progression. The literature had many anticancer agents containing benzimidazole cores that gained much interest. Provoked by our endless...

Investigation of cholinesterase and α-glucosidase enzyme activities, and molecular docking and dft studies for 1,2-disubstituted cyclopentane derivatives with phenyl and benzyl units

Six known products (4–9) were prepared from reaction of adipoyl chloride with 1,2,3-trimethoxybenzene according to the literature. From (2,3,4-trimethoxyphenyl)(2-(2,3,4-trimethoxyphenyl)cyclopent-1-en-1-yl)methanone (4) of them, four new 1,2-disubstituted cyclopentane derivatives (10–13) with phenyl and benzyl units were synthesized by reactions such as hydrazonation, catalytic...

One-pot synthesis, characterization and antiviral properties of new benzenesulfonamide-based spirothiazolidinones

A novel series of benzenesulfonamide substituted spirothiazolidinone derivatives (3a–j) were synthesized, characterized and evaluated for their antiviral activity. The spirocyclic compounds were prepared by the condensation of 4-(aminosulfonyl)-2-methoxybenzohydrazide, appropriate cyclic ketones and 2-mercaptopropionic acid in a one-pot reaction. The structures of the new...

Synthesis, molecular docking and molecular dynamics simulations, drug-likeness studies, ADMET prediction and biological evaluation of novel pyrazole-carboxamides bearing sulfonamide moiety as potent carbonic anhydrase inhibitors

Pyrazoles are unique bioactive molecules with a versatile biological profile and they have gained an important place on pharmaceutical chemistry. Pyrazole compounds containing sulfonamide nuclei also attract attention as carbonic anhydrase (CA) inhibitors. In this study, a library of pyrazole-carboxamides were synthesized and the structures of the synthesized molecules were...

FDI-6 inhibits VEGF-B expression in metastatic breast cancer: a combined in vitro and in silico study

Angiogenesis is the process by which new blood vessels are formed to meet the oxygen and nutrient needs of tissues. This process is vitally important in many physiological and pathological conditions such as tumor growth, metastasis, and chronic inflammation. Although the relationship of FDI-6 compound with FOXM1 protein is well known in the literature, its relationship with...