Abdul Hameed

Solid support catalysts and their applications in synthetic chemistry provide advantages, including significant catalytic efficiency and reduced environmental impact. Alkali and alkaline earth metals have received attention owing to their benign, cost‐effective nature, as well as being eco‐friendly and free from heavy metal disposal concerns. Compared to transition metal salts, such factors make alkali and alkaline earth metals an attractive alternative for catalytic applications. Based on these factors, herein, the solid‐supported catalysts were prepared by adsorbing alkali and alkaline earth metal (Na, K, Mg, Ca, and Ba) salts on silica gel, molecular sieves, and activated charcoal. The catalyst's efficacy was explored by employing it in the synthesis of N ‐heterocyclic acridine‐1,8‐diones ( 4a–d ) through multicomponent reaction. Optimization studies were carried out and further demonstrated via Box–Behnken design (BBD). The effects of three variables, including catalyst loading, temperature, and reaction time, were studied. The response surface and contour plots were developed to demonstrate optimal conditions in the preparation of acridine‐1,8‐diones. The BBD predicted and actual yields, determined by the optimal amount of catalyst, temperature, and reaction time, validate the significance of the study. Structure optimization as well as molecular electrostatics potential (MEP) of acridine‐1,8‐diones ( 4a–d) were also performed via density functional theory (DFT) analysis.

Aldehyde reductase (ALR1) is the enzyme that speeds up the reduction of many types of aldehydes into sorbitol and D-glucose. The essential enzyme of the polyol pathway, aldose reductase (ALR2), is responsible for the development of chronic complications associated with diabetes when activated under hyperglycemic conditions. Since it is a crucial mediator for the oxidative and inflammatory signaling pathways, ALR is thought to be a target for various diseases. Many medicines are available for the treatment of ALR-associated issues but due to their long term side-effects they are not effectively used. Coumarin is a naturally occurring compound, and its derivatives are widely used in the treatment of many ailments. Therefore, in the pursuit to find potential alternate candidates as drug leads, we have prepared new coumarin-based Schiff base analogues using DABCO-C ₇ -F ionic liquid and compared with conventional method. The sustainable approach making use of DABCO-C ₇ -F ionic liquid, not only made the synthesis easier but also it is cost- and time-effective. The synthesized analogues were further examined for their potentials against ALR2 (IC₅₀ = 1.61 to 11.20 µM) as well as checked selectivity via screening against ALR1 enzyme. Moreover, the molecular docking study was performed to elucidate the binding interactions of active compounds. The results showed that the synthesized compounds may have the potential to be further studied as new and selective anti-diabetic agents.

Alzheimer's disease (AD) is a multifactorial irreversible neurological disorder with multiple enzymes involved. In the treatment of AD, multifunctional agents targeting cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors have shown promising results. Herein, a series of novel quinoline–sulfonamides (a1–18) were designed and synthesized as a dual inhibitor of MAOs and ChEs. The in vitro results showed that compounds a5, a12, a11, and a6 exhibited the most potent compounds against specific enzymes. They had IC₅₀ value 0.59 ± 0.04 for MAO-A, 0.47 ± 0.03 for MAO-B, 0.58 ± 0.05 for BChE and 1.10 ± 0.77 for AChE μM respectively. Furthermore, kinetic studies revealed that these compounds are competitive. Molecular docking studies enhanced the understanding of the in silico component, unveiling critical interactions, specifically the hydrogen bonding interaction, π–π, π–alkyl, π–amid and π–sulfur interactions between the ligand and enzymes. These findings suggest that compounds a5, a6, a11, a12, a15, and a18 may be potent multifunctional candidates for AD treatment.

Ultraviolet-A (UVA) radiation is a major contributor to reactive oxygen species (ROS), reactive nitrite species (RNS), inflammation, and DNA damage, which causes photoaging and photocarcinogenesis. This study aimed to evaluate the UVA protective potential of lipophilic chain conjugated thiourea-substituted aryl group molecules against UVA-induced cellular damages in human dermal fibroblasts (BJ cell line). We tested a series of nineteen (19) molecules for UVA photoprotection, from which 2′,5′-dichlorophenyl-substituted molecule DD-04 showed remarkable UVA protection properties compared to the reference (benzophenone). The results indicate that DD-04 significantly reduced intracellular ROS and nitric oxide (NO) as compared to the UVA-irradiated control (p < 0.001). Moreover, the compound DD-04 showed anti-inflammatory activity as it significantly reduced the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) pro-inflammatory cytokines produced by THP-1 (human monocytic) cells (p < 0.05). DNA damage was also prevented by DD-04 treatment in the presence of UVA. It was observed that DD-04 significantly reduced the number of cyclobutane pyrimidine dimers (CPDs) when compared to the UVA-irradiated control (p < 0.001). Finally, the DNA strand breaks were checked and a single intact DNA band was seen upon treatment with DD-04 in the presence of UVA. In conclusion, DD-04 can be considered a potential candidate UVA filter due to its photoprotective potential.

The rapid development of resistance by ureolytic bacteria which are involved in various life-threatening conditions such as gastric and duodenal cancer has induced the need to develop a new line of therapy which has anti-urease activity. A series of pyridine carboxamide and carbothioamide derivatives which also have some novel structures were synthesized via condensation reaction and investigated against urease for their inhibitory action. Among the series, 5-chloropyridine-2 yl-methylene hydrazine carbothioamide (Rx-6) and pyridine 2-yl-methylene hydrazine carboxamide (Rx-7) IC50 = 1.07 ± 0.043 µM, 2.18 ± 0.058 µM both possessed significant activity. Furthermore, molecular docking and kinetic studies were performed for the most potent inhibitors to demonstrate the binding mode of the active pyridine carbothioamide with the enzyme urease and its mode of interaction. The ADME profile also showed that all the synthesized molecules present oral bioavailability and high GI absorption.

Excretion of heavy metals especially mercury (Hg²⁺⁾ from the industries into the environment becomes a major global problem. In this context, mercury is a highly dangerous metal which poses serious impact on human health. In the present study, acridine- (ACR-) based silver nanoparticles (ACR-AgNPs) were prepared and employed as a nanosensor for effective detection and quantification of Hg²⁺ in tap water. Conjugation between ACR-based coating agent and silver was examined by UV-visible and FT-IR spectroscopy, while morphology and particle size were determined through atomic force microscopy (AFM), dynamic light scattering (DLS), and scanning electron microscopy (SEM). Furthermore, sensing behavior of nanosensor for metal ions was evaluated by mixing different metals such as Mn²⁺, Ni²⁺, Ba²⁺, Mg²⁺, Cr³⁺, Pb²⁺, Pd²⁺, Al³⁺, Sn²⁺, Fe²⁺, Co²⁺, Cu²⁺, Fe³⁺, Cd²⁺, and Hg²⁺with ACR-AgNPs. Among all the added metal ions, only Hg²⁺resulted in significant quenching in the absorption intensity of ACR-AgNPs. The limit of detection of the ACR-AgNP-based nanosensor was found to be 1.65μM in a wide pH range (1-14). The proposed mercury sensor worked efficiently in the presence of other interfering agents such as other metal ions. Therefore, the synthesized ACR-AgNPs have proved to be an efficient and robust nanosensor for quantitative detection of Hg²⁺ in real sample analysis such as tap water. The proposed method does not require expensive instrumentation and trained manpower.

A targeted delivery system is primarily intended to carry a potent anticancer drug to specific tumor sites within the bodily tissues. In the present study, a carrier system has been designed using folic acid (FA), bis-amine polyethylene glycol (PEG), and an anticancer drug, 5-fluorouracil (5-FU). FA and PEG were joined via an amide bond, and the resulting FA-PEG-NH₂ was coupled to 5-FU producing folate-polyethylene glycol conjugated 5-fluorouracil (FA-PEG-5-FU). Spectroscopic techniques (UV-Vis, ¹HNMR, FTIR, and HPLC) were used for the characterization of products. Prodrug (FA-PEG-5-FU) was analyzed for drug release profile (in vitro) up to 10 days and compared to a standard anticancer drug (5-FU). Folate conjugate was also analyzed to study its folate receptors (FR) mediated transport and in vitro cytotoxicity assays using HeLa cancer cells/Vero cells, respectively, and antitumor activity in tumor-bearing mice models. Folate conjugate showed steady drug release patterns and improved uptake in the HeLa cancer cells than Vero cells. Folate conjugate treated mice group showed smaller tumor volumes; specifically after the 15th day post-treatment, tumor sizes were decreased significantly compared to the standard drug group (5-FU). Molecular docking findings demonstrated importance of Trp138, Trp140, and Lys136 in the stabilization of flexible loop flanking the active site. The folic acid conjugated probe has shown the potential of targeted drug delivery and sustained release of anticancer drug to tumor lesions with intact antitumor efficacy.

Urease has become an important therapeutic target because it stimulates the pathogenesis of many human health conditions, such as pyelonephritis, the development of urolithiasis, hepatic encephalopathy, peptic ulcers, gastritis and gastric cancer. A series of alkyl chain-linked thiourea derivatives were synthesized to screen for urease inhibition activity. Structure elucidation of these compounds was done by spectral studies, such as IR, ¹H NMR and ¹³C NMR, and MS analysis. In vitro urease enzyme inhibition assay revealed that compound 3c was the most potent thiourea derivative among the series with IC₅₀ values of 10.65 ± 0.45 μM, while compound 3g also exhibited good activity with an IC₅₀ value of 15.19 ± 0.58 μM compared to standard thiourea with an IC₅₀ value of 15.51 ± 0.11 μM. The other compounds in the series possessed moderate to weak urease inhibition activity with IC₅₀ values ranging from 20.16 ± 0.48 to 60.11 ± 0.78 μM. The most potent compounds 3c and 3g were docked to jack bean urease (PDB ID: 4H9M) to evaluate their binding affinities and to find the plausible binding poses. The docked complexes were refined through 100 ns-long MD simulations. The simulation results revealed that the average RMSD of 3c was less than that of the 3g compound. Furthermore, the radius of gyration plots for both complexes showed that 3c and 3g docking predicted binding modes did not induce any conformational change in the urease structure.

The applications of solid support catalysts in catalyzing organic reactions are well-evident. In the present study, we explored a transition metal fluoride (FeF₃) adsorbed on molecular sieves (4 Å) as a solid support catalyst for the preparation of sulfonamides 3a–3o. The solid support catalyst was characterized via X-ray diffraction and AFM analysis. The catalyst was further explored for the synthesis of indoles 6a–h, 1H-tetrazoles and 1,4-dihydropyridines. The sulfonamides prepared herein were investigated for their potential to inhibit carbonic anhydrase (hCA II, hCA IX and hCA XII). All compounds were found to be active inhibitors with IC₅₀ values in the low micromolar range. Some compounds were even found to be highly selective inhibitors. Compound 3i only inhibited hCA II (IC₅₀ = 2.76 ± 1.1 μM) and had 3e (IC₅₀ = 0.63 ± 0.14 μM) only inhibited hCA XII and showed 3e and 3i can provide significant leads for the further development of highly selective CA inhibitors.