The purpose is to synthesize a new class of furan-based chalcone compounds (KD1-KD14) and to investigate their monoamine oxidase (MAO)-A and -B inhibitory activities.

Misuse of central nervous system (CNS) depressants (alprazolam, fentanyl, etc.) is a major cause of fatal overdose, with a high prevalence of deaths involving polydrug interactions from the victim's own prescriptions. Thus, there is an urgent need to improve the safety of CNS depressants to prevent fatalities. Pharmacological pursuits aiming to prevent harm through the design of non-addictive alternatives have either failed before clinical trials or produced mediocre treatment alternatives. Therefore, we propose a new perspective for medicinal chemists: rather than aiming to prevent misuse, we must design new central nervous system (CNS) depressants under the expectation of misuse. By shifting the design focus to partial modulators rather than full agonists, we can develop novel chemical entities (NCEs) that intrinsically minimize physical harm caused by misuse without sacrificing therapeutic efficacy. In this perspective, we provide an overview of the two most widely misused classes of medications (opioid and GABA receptor modulators) in relation to pharmacodynamic properties and clinical outcomes. We then suggest a drug discovery pathway focused on physiological parameters. It is our opinion that this approach would dramatically decrease the lethality of overdose and improve outcomes of treatments for pain, anxiety, and withdrawal from alcohol, benzodiazepines, and opioids.

Cobra venom phospholipase A (PLA) has been known to induce life threatening effects post-envenomation in the victims. Being the most abundant and noxious component of snake venom, present study was envisaged to investigate new drug candidates against PLA enzyme.

This study focused on the synthesis, antimicrobial, and antileishmanial evaluation of seven amide derivatives ( to ). The target compounds were synthesized from cysteine methyl ester and various substituted aromatic and aliphatic carboxylic acids. The final products were characterized using physical and spectro-analytical techniques (FT-IR, H NMR). The derivatives were evaluated for their antimicrobial activity at various concentrations. Experimental studies revealed that compounds and were the most potent against and , exhibiting 18 mm and 21 mm inhibition zones, respectively, at a concentration of 2000 µg/mL. Additionally, and showed significant activity against , with 20 mm and 23 mm inhibition zones, respectively, at a concentration of 1000 µg/mL. The compounds also exhibited moderate to good activity against . Compounds , and demonstrated good activity, with IC values of 0.68 ± 0.09, 0.68 ± 0.16, 0.66 ± 0.08, and 0.68 ± 0.12 µg/mL, respectively. Molecular docking, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis, and Density Functional Theory (DFT) studies were conducted on the most potent compounds ( and ) to validate and support their experimental antimicrobial and antileishmanial potential.

(rat sarcoma) is one of the most frequently mutated gene families in cancer, encoding proteins classified as small GTPases. Mutations in RAS proteins result in abnormal activation of the RAS signaling pathway, a key driver in the initiation and progression of various malignancies. Consequently, targeting RAS proteins and the RAS signaling pathway has become a critical strategy in anticancer therapy. While RAS was historically considered an "undruggable" target, recent breakthroughs have yielded inhibitors specifically targeting KRAS and KRAS mutations, which have shown clinical efficacy in patients. However, these inhibitors face limitations due to rapid acquired resistance and the toxic effects of combination therapies in clinical settings. Targeted protein degradation (TPD) strategies, such as PROTACs and molecular glues, provide a novel approach by selectively degrading RAS proteins, or their upstream and downstream regulatory factors, to block aberrant signaling pathways. These degraders offer a promising alternative to traditional inhibitors by potentially circumventing resistance and enhancing therapeutic precision. This review discusses recent advancements in RAS pathway degraders, with an emphasis on targeting RAS mutations as well as their upstream regulators and downstream effectors for potential cancer treatments.

To explore the potent anti-inflammatory and anti-tuberculosis potential of novel trimetallic Au-Pt-Cu nanofluids.

This study aimed to synthesize and characterize a Schiff base ligand, (Z)-2-(2-oxoindolin-3-ylidene)hydrazinecarbothioamide (1), and its copper(II) (2) and zinc(II) (3) complexes, as well as evaluate their binding interactions with the epidermal growth factor receptor (EGFR) and anticancer activity against the human lung cancer A549 cell line.

To synthesize and characterize a Schiff base derived from vanillin and tris(hydroxymethyl)aminomethane (VTRIS) and the Zinc (II) complex [Zn(VTRIS)](CHCOO).

Lung cancer is the most prevalent invasive malignancy and the leading cause of cancer-related death. Chemotherapy is vital for lung cancer therapy, but multidrug resistance is responsible for the majority of lung cancer fatalities, creating an imperative demand to develop novel chemotherapeutics. Indole is a valuable anti-lung cancer pharmacophore since its derivatives could act on lung cancer cells through various mechanisms. Notably, indole hybrids could inhibit multiple targets simultaneously and have the potential to overcome the shortcomings of traditional chemotherapeutics. Moreover, many indole hybrids such as the indole-pyrimidine hybrid osimertinib and the indole-hydroxamic acid hybrid panobinostat, are either under clinical evaluations or have already been approved for lung cancer therapy. This indicates that the rational design of indole hybrids represents a highly prospective approach for the development of new anti-lung cancer chemotherapeutic agents. This review focuses on exploring the anti-lung cancer therapeutic potential of indole hybrids and delves into their action mechanisms as well as structure-activity correlations, covering articles published between 2021 and present. The ultimate goal is to offer a foundation for the rational design of indole hybrids in the future.

Lung cancer has become the most prevalent cancer for the past three decades, and the 5-years survival rate of lung cancer is only ~20% nowadays. Chemotherapy is the mainstay of lung cancer therapy, especially for non-small cell lung cancer. However, drug resistance represents a principal cause of therapeutic failure in non-small cell lung cancer leading to therapeutic insensitivity, tumor recurrence, and disease progression. Indole hybrids have the potential to conquer drug resistance, enhance efficacy, reduce adverse events, and improve pharmacokinetic properties due to their capacity to inhibit multiple targets simultaneously. Moreover, indole hybrids osimertinib, mobocertinib, cediranib, and vizimpro are currently applied in clinics for lung cancer therapy, demonstrating that indole hybrids are valuable scaffolds in the treatment and eradication of lung cancer. This review provides a comprehensive overview of the evolving landscape of indole hybrids with the in vitro and in vivo efficacy against lung cancer, and the structure-activity relationships as well as mechanisms of action are also discussed, covering articles published from 2021 onward.

Embracing structure extension and substitution variation, methylpyrazolones and dimethylpyrazoles were synthesized as VEGFR-2/HSP90 dual inhibitors.

The rapidly growing interest in the literature about the anticancer activity of 3,5-disubstituted pyrazolines and their promising therapeutic potentials/pharmacological properties, supported by the number of pyrazoline derivatives currently in clinical use or clinical trials, encouraged us to review the antiproliferative effects and biochemical investigations of probable mechanisms of action. Nevertheless, many reported pyrazoline-bearing compounds have anticancer activity without an explored mode of action, which opens new research avenues to examine their biochemical profiles further. Therefore, 3,5-disubstituted pyrazoline is a promising core that can be used to design new derivatives with anticancer activity based on the structure-activity relationship summarized in this review to obtain higher potency and selectivity.

TB drug discovery needs scientists' attention since drug resistance in TB, including extensively drug-resistant TB (XDR-TB) and multidrug-resistant TB (MDR-TB), is a major healthcare concern. Since millions of fatalities from tuberculosis are recorded each year, there is an urgent need to discover new anti-tubercular medications that will either eradicate or control the disease. Spiro compounds have garnered a lot of attention in medicinal chemistry these days because of various biological activities mainly because of their adaptability and structural resemblance to significant pharmacophores. This article overviews the synthesis and activity of spirocyclic compounds as anti-tubercular agents. Both synthesized and naturally occurring spiro chemicals exhibit antitubercular properties. The promising antitubercular potential shown by some of the spirocyclic compounds has attracted scientists to explore them further to develop molecules with improved pharmacodynamic and pharmacokinetic properties and new mechanisms of action with enhanced safety and efficacy in tuberculosis. The current review covers the exploration of spiro compounds from the year 2004 to 2024 for the combat of Tuberculosis. This review gives the comprehensive advancements in this scaffold which would help the logical design of powerful, less toxic, and more effective spirocyclic anti-TB medicinal molecules.

The review discusses progress in discovering cyclin-dependent kinase 2 (CDK2) inhibitors for cancer treatment and their potential for male contraception. It summarizes first-, second-, and third-generation CDK inhibitors and selective CDK2 inhibitors currently in clinical trials for cancer. Novel strategies to discover allosteric inhibitors, covalent inhibitors, and degraders are also discussed.

Thieno-pyrimidine derivatives have emerged as promising candidates for VEGFR-2 inhibition. This study aimed to design, synthesize, and evaluate novel thieno-pyrimidine derivatives for their anti-cancer potential.