A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-3-carboxylates 4a–f and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylates 4g–k have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of Mycobacterium tuberculosis by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8–128 µg/mL against H37Rv. The test compound dimethyl-1-(4-fluorobenzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylate 4j emerged as the most promising anti-TB agent against H37Rv and multidrug-resistant strains of Mycobacterium tuberculosis at 8 and 16 µg/mL, respectively. In silico evaluation of pharmacokinetic properties indicated overall drug-likeness for most of the compounds. Docking studies were also carried out to investigate the binding affinities as well as interactions of these compounds with the target proteins.

Oxidative stress and inflammation are implicated in depression. While selective serotonin reuptake inhibitors (SSRIs) like escitalopram are commonly prescribed as first-line treatments, their inconsistent efficacy and delayed onset of action necessitates the exploration of adjunctive therapies. Isorhamnetin, a flavonol, has shown antioxidant and anti-inflammatory properties that makes exploring its antidepressant effect attractive. This study aims to investigate the adjuvant potential of isorhamnetin in combination with escitalopram to enhance its antidepressant efficacy in a lipopolysaccharide (LPS)-induced depression model using Swiss albino mice. Behavioral paradigms, such as the forced swim test and open field test, were employed to assess depressive symptoms, locomotion, and sedation. Additionally, enzyme-linked immunosorbent assays were utilized to measure Nrf2, BDNF, HO-1, NO, and IL-6 levels in the prefrontal cortex and hippocampus. The results demonstrate that isorhamnetin significantly improves the antidepressant response of escitalopram, as evidenced by reduced floating time in the forced swim test. Moreover, isorhamnetin enhanced antidepressant effects of escitalopram and effectively restored depleted levels of Nrf2, BDNF, and HO-1 in the cortex caused by LPS-induced depression. Isorhamnetin shows promise in enhancing the efficacy of conventional antidepressant therapy through antioxidant and anti-inflammatory effects.

Background and Objectives: The current war on the Gaza strip and the circulating violent content is believed to negatively impact the mental health of the Palestinians living in refugee camps outside their homeland. This study explores the prevalence and correlates of depression, anxiety, and insomnia in a cohort of female Palestinian refugees in Jordan who have family members entangled in the persistent conflict in the Gaza strip. Materials and Methods: This cross-sectional study employed validated tools to assess depression, anxiety, and insomnia in women residing in a Gaza camp located in Jerash, Jordan. The correlates were determined by regression analysis. Results: The study unearths disconcerting statistics from 177 recruited women, revealing alarmingly high rates of severe depression (73%), anxiety (60%), and insomnia (65%). Multivariable analysis revealed that severe depression was significantly associated with prior diagnosis with chronic diseases (OR = 3.0, CI = 1.36–6.58), and having a first-degree relative in Gaza (OR = 0.42, CI = 0.20–0.85). Additionally, severe insomnia was associated with “losing relatives or friends in the war” (OR = 3.01, CI = 1.41–6.44), and “losing connection with families and friends” (OR = 3.89, CI = 1.58–9.53). Conclusions: The implications of these results are profound, underscoring the immediate and imperative need for both medical and psychiatric interventions aimed at addressing the substantial psychological burden borne by this population because of the ongoing conflict.

A series of 17 compounds (12–16 b) with 2,4,5-trisubstitutedthiazole scaffold having 5-aryl group, 4-carboxylic acid/ester moiety, and 2-amino/amido/ureido functional groups were synthesised, characterised, and evaluated for their carbonic anhydrase (CA)-III inhibitory activities using the size exclusion Hummel–Dreyer method (HDM) of chromatography. Compound 12a with a free amino group at the 2-position, carboxylic acid moiety at the 4-position, and a phenyl ring at the 5-position of the scaffold was found to be the most potent CA-III inhibitor (K_i = 0.5 μM). The presence of a carboxylic acid group at the 4-position of the scaffold was found to be crucial for the CA-III inhibitory activity. Furthermore, replacement of the free amino group with an amide and urea group resulted in a significant reduction of activity (compounds 13c and 14c, K_i = 174.1 and 186.2 μM, respectively). Thus, compound 12a (2-amino-5-phenylthiazole-4-carboxylic acid) can be considered as the lead molecule for further modification and development of more potent CA-III inhibitors.

Background: Thieno[2,3-c]pyridines and their analogs are not well explored for their anticancer properties. Hence, our research aimed to establish the anticancer potential of thieno[2,3-c]pyridines through cell-based assays and in silico evaluations. Methods: Thieno[2,3-c]pyridine derivatives 6(a–k) were synthesized and characterized using FT-IR, ¹H-NMR, ¹³C-NMR, and HRMS. All the synthesized compounds were screened initially for their anticancer activity against MCF7 and T47D (breast cancer), HSC3 (head and neck cancer), and RKO (colorectal cancer) cell lines using MTT assay. Apoptosis and cell cycle analyses were conducted using Annexin V/propidium iodide (PI) double staining for apoptosis assessment and PI staining for cell cycle analysis to investigate the mechanisms underlying the reduced cell viability. In silico molecular docking was accomplished for the synthesized compounds against the Hsp90 and determined pharmacokinetics properties. Results: From the screening assay, compounds 6a and 6i were identified as potential inhibitors and were further subjected to IC₅₀ determination. The compound 6i showed potent inhibition against HSC3 (IC₅₀ = 10.8 µM), T47D (IC₅₀ = 11.7 µM), and RKO (IC₅₀ = 12.4 µM) cell lines, all of which indicated a broad spectrum of anticancer activity. Notably, 6i was found to induce G2 phase arrest, thereby inhibiting cell cycle progression. Molecular docking results indicated crucial molecular interactions of the synthesized ligands against the target Hsp90. Conclusion: The compound 6i induced cell death via mechanisms that are different from apoptosis. Thus, the synthesized thieno[2,3-c]pyridine derivatives can be suitable lead compounds to be optimized to obtain potent anticancer agents through Hsp90 inhibition.

Background: Recently, a series of 15 compounds with 2,4,5-trisubstitutedthiazole scaffold having 2- amino/amido/ureido functional groups attached with 5-aryl and 4-carboxylic acid/ester groups (1-15) were reported from our research group as novel potential inhibitors of carbonic anhydrase III (CA III) enzyme. Several research studies revealed the potential role of CA inhibitors as anticancer agents, giving us the impetus to further explore these compounds for their potential as anticancer agents. Objectives: The objective of this study is to investigate the potential of 2,4,5-trisubstitutedthiazole derivatives (1-15) for their possible cytotoxic activity (in vitro), and to calculate (in silico) the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties to evaluate the drug-likeness of these compounds. Methods: Cytotoxic activity (in vitro) was carried out on two breast cancer cell lines (MCF7 and MDA231), and the lymphoblastoid human erythroleukemia cell line (K562) using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Doxorubicin was used as a positive control. ADMET properties were calculated (in silico) using the QikProp module of Schrodinger. Results: Compounds 6 and 9 with a phenylureido group at 2-position, and a methyl-carboxylate moiety at 4-position having para-tolyl and benzyl moiety, respectively at the 5-position of the thiazole ring showed significant cytotoxicity against all the three cell lines. In particular, compound 6 with para-tolyl group at 5-position exhibited the most potent inhibitory effect on the viability of MCF7, MDA231 and K562 cells, with IC₅₀ values of 22, 26 and 11 μM, respectively. Notably, all the highly active compounds possess a phenyluriedo group at 2-- position with a methyl ester group at 4-position, indicating the probable role of these substituents in the target interaction and inducing cytotoxicity. Interestingly, compounds 1-4 and 10-13 with a free amino group at 2-position did not show any cytotoxic effect on the K562 cell line, while exhibiting mild to moderate cytotoxicity against the MCF7 and MDA231 cell lines. However, none of the tested compounds showed any activity against normal human dermal fibroblast cells indicating the safety/tolerability of the examined concentrations. Furthermore, these compounds also exhibited satisfactory ADMET properties (in silico), without violating Lipinski’s rule of five. Conclusion: The most active compounds 6 and 9 predicted to have good oral absorption and low human serum protein binding, exhibiting no reactive functional group and probable CNS activity compared with 95% of the known oral drugs as predicted (in silico) by QikProp. Thus, compounds 6 and 9 can be considered as lead molecules for further modification and discovery of novel anticancer agents with nanomolar potency.