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In the 21st century, pathogenic deformities contribute significantly to global morbidity and mortality. Our research investigates the antimalarial, antimicrobial, and antioxidant activities of newly synthesized hydrazones and their organotin (IV) complexes, derived from 2‐benzoyl‐1H‐indene‐1,3(2H)‐dione and 2‐phenoxypropanehydrazide/2‐(2,4‐dichlorophenoxy)propanehydrazide. Structural confirmation was achieved through multinuclear nuclear magnetic resonance (NMR), UV–Vis, IR, HRMS, thermogravimetric analysis (TGA), and scanning electron microscopy (SEM)‐energy‐dispersive X‐ray analysis (EDAX), revealing tridentate coordination of ligands to the tin metal via imine nitrogen and two enolic oxygens, forming a pentacoordinated geometry. The SEM analysis revealed that hydrazone ligand (1) exhibits a rectangular bar‐like microstructure, whereas its complex (5) shows a rugged surface with distinct territorial patches. Compounds (5) [Bu2SnL1] and (6) [Ph2SnL1] stood out with significant bioactivity, with antimalarial IC50 values ranging from 0.54 ± 0.07 to 0.67 ± 0.06 μM and antioxidant IC50 values from 4.39 ± 0.02 to 4.67 ± 0.01 μM. Additionally, compounds (6) [Ph2SnL1] and (10) [Ph2SnL4] exhibited the highest antimicrobial activity, with MIC values ranging from 0.0045 to 0.0042 μmol/mL, respectively, comparable to standard drugs. Complementing the experimental data, in silico molecular docking studies were performed on the most effective ligand (1) [H2L1] and its phenyl complex (6) [Ph2SnL1] with Plasmodium falciparum lactate dehydrogenase, revealing binding energies of −6.0 and −6.9 kcal/mol, respectively, and corroborating the experimental findings. Further, comprehensive absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluations were performed on each compound to gauge their suitability as drug candidates and potential for toxicity. [ABSTRACT FROM AUTHOR]

Malaria, a persistent and ancient adversary, continues to impact vast regions worldwide, afflicting millions and severely affecting human health and well‐being. Recently, despite significant progress in combating this parasitic disease, malaria remains a major global health concern, especially in areas with limited resources and vulnerable populations. Consequently, identifying and developing effective agents to combat malaria and its associated dysfunctions is essential therefore the two new Schiff base ligands incorporated Co(II), Ni(II), Cu(II) and Zn(II) ions were synthesized and thoroughly characterized. The synthesized compounds were assessed for in vitro anti‐malarial and antimicrobial efficacy, compounds (9, 10) demonstrated highest potential with IC50=1.08±0.09 to 1.18±0.04 μM against P. falciparum and MIC=0.0058 μmol/mL against C. albicans and E. coli, respectively. The complexes (5, 6) were effectively reduce mitigate oxidative stress with lowest IC50 value of 2.69±0.12 to 2.87±0.09 μM. Moreover, the biological findings were reinforced by a molecular docking investigation involving the potential compounds (2, 7–10) against dihydroorotate dehydrogenase and sterol 14‐alpha demethylase proteins which exposed complex's excellent biological response than their parent ligands. ADMET profiling was used to confirm the compounds' oral drug‐like features. This research offers promising prospects for future multi‐functional drug innovations targeting malaria, pathogenic infections, and oxidative stress. [ABSTRACT FROM AUTHOR]

New diorganotin(IV) complexes (R2SnL, where R is Me, Et, Bu, and Ph) of Schiff base ligands N'-(2-hydroxybenzylidene)-3-methoxybenzohydrazide (H2L1), N'-(5-chloro-2-hydroxybenzylidene)-3-methoxybenzohydrazide (H2L2), N'-(2-hydroxy-5-nitrobenzylidene)-3-methoxybenzohydrazide (H2L3), and N'-(4-(diethylamino)-2-hydroxybenzylidene)-3-methoxybenzohydrazidefrom (H2L4) derived from 3-methoxybenzohydrazide with salicylaldehyde and its derivatives were synthesized. The ligands and their metal complexes were structurally characterized by spectroscopic techniques (FT-IR, 1H, 13C, and 119Sn NMR), elemental analysis, mass spectrometry, melting point, and molar conductance studies. The spectral data showed that ligands are coordinated to the tin atom in a tridentate manner with N and O donor sites of the azomethine-N, enolic-O, and aromatic hydroxyl-O to form a penta-coordinated geometry around central tin atom. The molar conductance data revealed that all compounds are non-electrolytes. In vitro antimicrobial activities of compounds were determined against various pathogens with reference to standard antibiotics which showed that compounds (12) (Ph2SnL2) and (16) (Ph2SnL3) are the most potent antimicrobial agents. Furthermore, the compounds were evaluated for antioxidant activity by using DPPH assay. The results obtained emphasized that the phenyl derivatives of complexes have enhanced antimicrobial and antioxidant activities as compared to other complexes. To check the drug-likeness, in silico studies of the synthesized compounds were carried out which described that all the compounds except (12) (Ph2SnL2), (19) (Bu2SnL4), and (20) (Ph2SnL4) can be used as orally active drugs. [ABSTRACT FROM AUTHOR]

New Co(II), Ni(II), Cu(II) and Zn(II) metal complexes of Schiff base ligands derived by the condensation of 6-aminoindazole with different derivatives of salicylaldehyde were synthesized and characterized. Further compounds were evaluated for antimicrobial, anti-inflammatory, antioxidant and molecular docking studies and findings results revealed that compound 12 exhibit higher potency, against antimicrobial and anti-inflammatory studies, whereas antioxidant activity revealed that the activity of Schiff base ligands enhanced on complexation with transition metal. [Display omitted] • Schiff base-derived hexacoordinated transition metal(II) complexes were synthesized and characterized. • The in vitro antimicrobial, anti-inflammatory and antioxidant activities were performed. • Complex 11 and 12 displayed potent biological activities. • Molecular docking, DFT and ADMET studies validated the in vitro results. Indazoles represent one of the most important heterocycles in drug molecules. Therefore, in the pursuit of potent biological agents, a series of ligands (HL1-HL4) and their corresponding transition metal complexes [M(L1-L4) 2 (H 2 O) 2 ] were synthesized by the condensation reaction of 6-aminoindazole with various derivatives of salicylaldehyde. Further, the compounds underwent characterization through several physicochemical (TGA, powder XRD, SEM, EDAX) and spectroscopic techniques (FT-IR, UV–Vis, NMR, mass spectrometry, ESR). These techniques suggested hexacoordinated stereochemistry of the metal complexes, where ligands chelate via oxygen atom of phenolic ring, azomethine nitrogen and oxygen atom of water molecules in 1:2 (M:L) molar ratio. The thermal stability of the complexes was demonstrated by thermal analysis revealing three step decompositions leaving behind metal oxide as an end residue. The surface morphology of the ligands was distinct from metal complexes as revealed by SEM analysis, while mapping images demonstrated the simultaneously existence of the elements. While, to ascertain the nature of the obtained compounds (crystalline or amorphous), powder X-ray investigation was conducted by utilizing a wavelength of 1.54 Å. The compound's antioxidant potential was assessed through DPPH assays and anti-inflammatory activity was evaluated using BSA denaturation inhibition assay, while their antimicrobial potential was evaluated against six microbial strains (E. coli, S. aureus , P. aeruginosa, B. subtilis , C. albicans, A. niger) by serial dilution approach. The performed biological evaluations revealed that the complexes are more efficient in controlling infectious ailment in comparison of ligands. HL2 (2) and its Cu(II), Zn(II) complexes (11, 12) exhibited potent antimicrobial activity (MIC value: 0.0047, 0.0048 µmol/mL against B. subtilis) and potent anti-inflammatory efficacy (IC 50 value: 6.7 ± 0.044, 6.9 ± 0.036 µM). All the complexes exhibited potent antioxidant activity and their is enhancement in the activity of Schiff base ligands upon complexation, complex (19) demonstrated the greatest activity with IC 50 value 2.1 ± 0.059. Additionally, the ADMET score provided a robust indication of the compounds' drug-like behaviour. Furthermore, the biological effectiveness of the highly microbial potent ligand HL2 (2) and its complexes (9–12) was demonstrated through computational studies. The binding studies exposed that complexes (11, 12) exhibited lowest binding energy at −7.8, −7.9 kcal/mol. While, DFT study emphasized that complex (12) exhibits the highest electrophilicity index value (6.359), suggesting its affinity for binding with biological molecules and also revealed that complexes exhibit greater potency compared to the ligands and could potentially be utilized as drugs for combatting pathogen-induced malformations. [ABSTRACT FROM AUTHOR]

We have synthesized new diorganotin(IV) complexes of the type R2SnL (where R; methyl, ethyl, butyl and phenyl) of Schiff base ligands N'-(5-chloro-2-hydroxybenzylidene)thiophene-2-carbohydrazide (H2L1), N'-(4-(diethylamino)-2-hydroxybenzylidene)thiophene-2-carbohydrazide (H2L2), N'-(3,5-dibromo-2-hydroxybenzylidene)thiophene-2-carbohydrazide (H2L3) and N'-(2-hydroxy-5-methoxy-3-nitrobenzylidene)thiophene-2-carbohydrazide (H2L4). Spectroscopic methods (FT-IR, UV–vis, 1H, 13C and 119Sn NMR), elemental analysis, mass spectrometry, melting point and molar conductance measurements were used to elucidate the structures of compounds (1-20). The spectroscopic data indicated that the Schiff bases are tridentate (NOO) in nature and coordinated to the tin metal through enolic oxygen, azomethine nitrogen and aromatic hydroxyl oxygen donor atoms to display pentacoordinated geometry around the central tin metal. To examine the biological profile, the synthesized compounds were tested for in vitro antimicrobial activity against different bacterial and fungal strains by using serial dilution method which revealed that compounds Bu2SnL3 (15) and Ph2SnL3 (16) were most active antimicrobial agent. The compounds were further tested for antioxidant activity by using DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Complex Ph2SnL3 (16) exhibited highest antioxidant potential with lowest IC50 value (2.95 μM) among all the tested compounds. [ABSTRACT FROM AUTHOR]

Synthesis, characterization, antimalarial, antioxidant and antimicrobial activities of four newly synthesized hydrazone ligands and their diorganotin(IV) metal complexes. [Display omitted] • This research work emphasizes study of hydrazone ligands and their diorganotin(IV) complexes. • The compounds were characterised by physical and spectral investigations. • The biological studies such as antimalarial, antioxidant and antimicrobial were carried out and further supported by in silico ADME studies. • The complexes (16,20) were most active against antimalarial and antioxidant. • Complexes (8, 12) were most potent against antimicrobial. Inspired by the role of organotin(IV) compounds as potential pharmaceutical agents, we have synthesized a series of new diorganotin(IV) complexes (5–20) of hydrazone ligands (1–4) derived from 2-chlorophenoxyacetic hydrazide and salicylaldehyde derivatives. Numerous techniques such as FT-IR, UV–Vis, (1H, 13C, 119Sn) NMR, mass spectrometry, powder XRD, SEM, EDAX, TGA and molar conductance were used to elucidate the structure of the synthesized compounds. These techniques ascertain that the hydrazone ligands coupled with diorganotin(IV) in a tridentate manner via imine nitrogen, phenolic oxygen atom and deprotonated hydroxyl group generating pentacoordinated geometry of the complexes. The low molar conductance values of synthesized compounds indicated their non-electrolytic nature. SnO 2 was the final product formed as a result of the thermal breakdown of complexes which suggested the thermal stability of the complexes up to about 176°C. In vitro antimalarial (P.falciparum) activity was performed using microassay protocol which advocated for the higher potency of complexes 16, 20 (IC 50 = 0.62–0.67 µM). The antioxidant activity also supported the results of antimalarial data suggesting 16, 20 complexes as active compounds. In vitro, the antimicrobial potential of the compounds has been tested against six pathogens including four bacterial and two fungal strains by serial dilution assay taking ciprofloxacin and fluconazole as reference drugs. Among the synthesized compounds, complexes 8 and 12 (MIC value = 0.0048, 0.0045 µmol/mL) exhibited superior activity. Additionally, the compounds were subjected to in silico ADME analysis suggesting that the compounds can be employed as orally active drugs. [ABSTRACT FROM AUTHOR]

• A series of four hydrazone ligands and their sixteen diorganotin(IV) complexes were synthesized and characterized. • Single crystal data revealed tridentate nature (ONO) of hydrazones forming a trigonal bipyramidal geometry. • Both the antioxidant and antimicrobial activity got enhanced upon complexation. • In silico ADME study demonstrated that the compounds can be used as orally active drugs. We have synthesized a series of four ligands (H 2 L1 - H 2 L4) and their sixteen diorganotin(IV) complexes R'' 2 SnL, [R'' = Me, Et, Bu, Ph]. The ligands were derived by condensation of 2-hydroxy-3-methylbenzohydrazide with different salicylaldehyde derivatives. The synthesized compounds were well characterized by various spectroscopic and physicochemical techniques like FT-IR, (1H, 13C, 119Sn) NMR, UV-Vis, SEM-EDAX, TGA, XRD, HRMS, molar conductance measurements and elemental analysis. The spectroscopic data suggested the tridentate nature (ONO) of hydrazones forming a pentacoordinated environment around the tin metal. Further, the X-ray crystallographic study of compound [Me 2 SnL4] (17) confirmed the anticipated results of tridentate (ONO) nature of ligands forming distorted trigonal bipyramidal geometry with the tin metal atom. The synthesized compounds were assessed for their in vitro antioxidant activity and compound [Ph 2 SnL1] (8) exhibited the best activity with IC 50 value of 2.92 µM. In vitro antimicrobial potential of the synthesized compounds was evaluated against different microbial strains viz. S. aureus, B. subtilis, p. aeruginosa, E. coli, C. albicans, A. niger. The antimicrobial data inferred that the complexes exhibited better efficacy than their parent ligands and compound [Et 2 SnL4] (16) exhibited the highest activity having same MIC value of 0.0053 µmol/mL against S. aureus and A. niger. Furthermore, in silico ADME study of the compounds was also carried out and observation revealed that the compounds can be used as an orally active drugs. Diorganotin(IV) complexes of 2-hydroxy-3-methylbenzohydrazide with salicylaldehyde derivatives were synthesized and characterized. Single crystal of compound [Me 2 SnL 4 ] (17) exhibited trigonal bipyramidal geometry and compounds were investigated for their antimicrobial, antioxidant and ADME studies. [Display omitted] [ABSTRACT FROM AUTHOR]

Exploring the therapeutic potential of the hydrazone ligands (1–2) and their transition metal complexes (3–10) against malarial and oxidant dysfunctions. The molecular docking and ADMET studies were performed to examine the medicinal abilities of the compounds. [Display omitted] • Hexacoordinated complexes and their ligand were investigated for antimalarial and antioxidant potential. • Complexes are more potent than ligand. • Complex (10) shows highest potency as pharmaceutical agent. • Molecular docking and ADMET studies well support the in vitro results. Malaria is a leading cause of death in many parts of the world and has a profound impact on public health and poses significant challenges to healthcare systems in endemic regions. Malaria is a severe and sometimes fatal disease caused by Plasmodium parasites and its one significant aspect of malaria pathophysiology is its relationship with oxidative stress, a condition characterized by an imbalance between the production of free radicals and the body's ability to detoxify these reactive products or repair the resulting damage. So, in the present research, to identify effective agents for malaria and oxidative stress, microassay and DPPH protocols were applied to previously synthesized and well characterized octahedral hydrazone ligands (1–2) and their Co(II), Ni(II), Cu(II), Zn(II) metal complexes (3–10), which were derived from 2-methoxy-1-naphthaldehyde, 3,5-bis(trifluoromethyl)benzohydrazide, 3-bromo-5-ethoxy-4-hydroxybenzaldehyde. The biological assessment indicated that complexes (8, 9, 10) were particularly effective in inhibiting malaria and oxidative infections as compared to other compounds. Among these, zinc(II) complex (10) exhibited the highest efficacy for malaria and oxidative stress, with an IC 50 values of 0.59 ± 0.13 and 2.12 ± 0.17 µM which are comparable with quinine and ascorbic acid, correspondingly. Additionally, molecular docking studies against the 8E1Z and 1U5A proteins along with ADMET investigations were also support the superior efficacy of complex (10), demonstrating the lowest binding affinity, favorable binding modes and drug likeness ability. [ABSTRACT FROM AUTHOR]