Medicinal Chemistry - Volume 21, Issue 1, 2025

Globally, parasitic diseases are considered among the neglected diseases. Clinically, several drugs are used in treatment, however due to drug resistance and multidrug resistance and the low investment in new research lines, there has been a failure in the treatment of parasitic illnesses.

The present mini-review is a comprehensive review of the use of platinum group metals as biological agents. It aims to establish the actual state of the art of these metal elements in the antiparasitic activity-specific area and define the future possibilities of action.

The review comprises more than 100 research works done in this field. The differences between platinum group metals chemistry and their use as metal complexes with biological activity have been discussed.

This review highlighted the platinum group metal's potential as an antiparasitic agent for different diseases.

The review will be helpful for the researchers involved in targeted drugs for parasitic disease therapy.

Thiophene is one of the most important heterocyclic scaffolds with notable pharmacological properties. Thiophene and its derivatives are of particular interest among sulphur-containing heterocycles because of their similarities to numerous natural and synthetic compounds with identified potential. The purpose of this study is to extensively analyse the synthetic pathways adopted for synthesising thiophene derivatives and investigate their various biological functions.

A comprehensive review of the existing literature was conducted to collect data pertaining to the methods that are employed for the synthesis of thiophene derivatives. A comprehensive search was carried out through relevant databases, including work published in 2024. A variety of synthesis procedures were identified and arranged, encompassing both traditional approaches like the Gewald reaction and contemporary ones like microwave-assisted synthesis and green synthesis. In addition, a comprehensive compilation of in vitro and in vivo studies was conducted to investigate the biological effects of 50 distinct thiophene derivatives. The primary focus of the studies was on various activities such as anti-cancer, anti-inflammatory, antiprotozoal, antibacterial, antioxidant, and antiviral functions.

Diverse methodologies have been employed in the synthesis of thiophene derivatives, encompassing both conventional and modern methods. Furthermore, the biological potential of thiophene derivatives was investigated, demonstrating a broad range of actions. Key structural elements necessary for biological activity were clarified by investigations of the structure-activity relationship.

The biological potential and flexible synthesis pathways of thiophene derivatives make them attractive candidates for use in medicinal and pharmaceutical chemistry. Understanding the different synthesis methods and biological actions of thiophene derivatives may assist rational design and create novel treatments for a variety of conditions. The potential for these compounds to be further explored and optimised is considerable for the next drug development initiatives.

Furoxan and benzofuroxan are compounds containing an N-oxide function, known for their diverse pharmacological properties, including antimicrobial and anti-inflammatory effects. This study aimed to investigate these activities using an in-house library of N-oxide compounds.

Twenty compounds were tested against both Gram-positive and Gram-negative bacteria, including Cutibacterium acnes (C. acnes), a microorganism implicated in the development of acne vulgaris. One compound, (E)-4-(3-((2-(3-hydroxybenzoyl)hydrazone)methyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazol-2-N-oxide (compound 15), exhibited selective antimicrobial activity against C. acnes, with a Minimum Inhibitory Concentration (MIC) value of 2 µg/mL. Indirect measurement of Nitric Oxide (NO) release showed that compound 15 and isosorbide dinitrate, when treated with L-cysteine, produced nitrite levels of 20.1% and 9.95%, respectively. Using a NO scavenger (PTIO) in combination with compound 15 in a culture of C. acnes resulted in reduced antimicrobial activity, indicating that NO release is part of its mechanism of action. Cytotoxicity assessments using murine macrophages showed cellular viability above 70% at concentrations up to 0.78 μg/mL.

Measurements of Interleukin-1 beta (IL1-β) and Tumor Necrosis Factor-alpha (TNF-α) indicated that compound 15 did not reduce the levels of these pro-inflammatory cytokines. Sustained NO production by inducible Nitric Oxide Synthase (iNOS) in macrophages or neutrophils has been found to be involved in the inflammatory process in acne vulgaris and lead to toxicity in surrounding tissues. Nitrite levels in the supernatant of murine macrophages were found to be decreased at a concentration of 0.78 μg/mL of compound 15, indicating an anti-inflammatory effect. In vivo studies were conducted using Balb/c nude mice inoculated subcutaneously with C. acnes. Cream and gel formulations of compound 15 were applied to treat the animals, along with commercially available anti-acne drugs, for 14 days. Animals treated with a cream base containing 5% of compound 15 exhibited less acanthosis with mild inflammatory infiltration compared to other groups, highlighting its anti-inflammatory properties.

Similar results were observed in the benzoyl peroxide group, demonstrating that compound 15 presented comparable anti-inflammatory activity to the FDA-approved drug. These promising results suggest that compound 15 has a dual mechanism of action, with selective antimicrobial activity against C. acnes and notable anti-inflammatory properties, making it a potential prototype for developing new treatments for acne vulgaris.

Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of Trypanosoma cruzi (α-TcCA) has emerged as an interesting target for the design of new antiparasitic compounds due to its crucial role in parasite processes.

The aim in this study was identify potential α-TcCA inhibitors with trypanocidal activity.

A maximum common substructure (MCS) and molecular docking were used to carried out a ligand- and structure-based virtual screening of ZINC20 and MolPort databases. The compounds selected were evaluated in an in vitro model against the NINOA strain of Trypanosoma cruzi, and cytotoxicity was determined in a murine model of macrophage cells J774.2.

Five sulfonamide derivatives (C7, C9, C14, C19, and C21) had the highest docking scores (-6.94 to -8.31 kcal/mol). They showed key residue interactions on the active site of the α-TcCA and good biopharmaceutical and pharmacokinetic properties. C7, C9, and C21 had half-maximal inhibitory concentration (IC50) values of 26, 61.6, and 49 μM, respectively, against NINOA strain epimastigotes of Trypanosoma cruzi.

Compounds C7, C9, and C21 showed trypanocidal activity; therefore, these results encourage the development of new trypanocidal agents based in their scaffold.

Chalcone compounds exhibit diverse bioactivities, attracting significant interest. Morpholine is a heterocycle commonly used in medicinal chemistry. It could enhance the potency, pharmacokinetics, and bioactivities of its compounds.

Adding morpholine into the chalcone scaffold could help create new compounds with favorable bioactivities. In this study, a new parallel synthesis procedure has been developed. Using this procedure, 18 novel morpholinoalkoxychalcones have been successfully synthesized. They had chains with morpholine appended on ring A or ring B. All the synthesized compounds were evaluated for the antibacterial and antifungal activities by agar diffusion method on 5 bacteria and 2 fungi strains.

The compounds with good inhibition were determined with respect to the MIC values by the agar dilution method. Among the tested compounds, B.21 was found to be the best against E. faecalis, with an MIC value of 0.6 mM. B.43 with an MIC value of 2.04 mM has displayed its potential in inhibiting A. niger and C. albicans the best among other compounds.

The in silico study has revealed two targets to align with the in vitro results. Longer alkyl chains have enhanced the activity, along with the presence of OH, NH2, and halogen groups on both rings A and B.

Flavonoids express a wide range of medicinal properties, our study presented results on the anticancer activity of selected compounds using in silico studies.

In this article, in silico studies were carried out to find promising anticancer lead among selected flavonoid compounds.

Here, we carried out molecular docking and MD simulation for anticancer screening of flavonoid derivatives against CDK2 and CDK9 proteins.

Among the compounds under investigation, Flavone and Recoflavone had the lowest binding energy against CDK2/CDK9 targets using docking studies and MD simulations.

We can conclude that Flavone and Recoflavone are promising anticancer lead compounds in the development of new anticancer drugs.