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Excessive and imbalance of free radicals within the body lead to inflammation. The objective of the current research work was to explore the anti-inflammatory and antioxidant potential of the isolated compounds from Habenaria digitata. In this study, the isolated phenolic compounds were investigated for in vitro and in vivo anti-inflammatory potential along with the antioxidant enzyme. The anti-inflammatory and antioxidant potential of the phenolic compounds was assayed via various enzymes like COX-1/2, 5-LOX and ABTS, DPPH, and H 2 O 2 free radical enzyme inhibitory assay. These compounds were also explored for their in vivo antioxidant activity like examining SOD, CAT, GSH-Px, and MDA levels in the brain, heart, and liver. The anti-inflammatory potential was evaluated using the carrageenan-induced pleurisy model in mice. On the basis of initial screening of isolated compounds, the most potent compound was further evaluated for the anti-inflammatory mechanism. Furthermore, the molecular docking study was also performed for the potent compound. The phenolic compounds were isolated and identified by GC-MS/NMR analysis by comparing its spectra to the library spectra. The isolated phenolic compounds from H. digitata were 5-methylpyrimidine-24,4-diol (1), 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (2), 2-isopropyl-5-methylphenol (3), 3-methoxy-4-vinylphenol ( 4 ), and 2,6-dimethoxy-4-vinylphenol (5). In in vitro antioxidant assay, the most potent compound was compound 1 having IC 50 values of 0.98, 0.90, and 5 μg/mL against ABTS, DPPH, and H 2 O 2 , respectively. Similarly, against COX1/2 and 5-LOX ,compound 1 was again the potent compound with IC 50 values of 42.76, 10.70, and 7.40 μg/mL. Based on the in vitro results, compound 1 was further evaluated for in vivo antioxidant and anti-inflammatory potential. Findings of the study suggest that H. digitata contains active compounds with potential anti-inflammatory and antioxidant effects. These compounds could be screened as drug candidates for pharmaceutical research, targeting conditions associated with oxidative stress and inflammatory conditions in medicinal chemistry and support their ethnomedicinal use for inflammation and oxidative stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Almasoudi, Saeed Jan, Nahari, Alhazmi, Binshaya, Abdulaziz, Mahnashi, Ibrar, Zafar and Sadiq.)

Isoxazole belongs to the class of five-membered heterocyclic compounds. The process of developing new drugs has significantly gained attention due to inadequate pharmacokinetic and safety attributes of the available drugs. This study aimed to design a new diverse array of ten novel isoxazole derivatives via Claisen Schmidt condensation reaction. In vitro COX-1/2 anti-inflammatory assay, in silico molecular docking of potent compounds, Molecular docking simulation, and SwissADME pharmacokinetic profile were investigated in this research. The in vitro COX-1 and COX-2 enzyme inhibitory assay showed that almost all the tested compounds exhibited anti-inflammatory effects whereas C6 , C5 , and C3 were found to be the most potent COX-2 enzyme inhibitors among the tested compounds and are good candidates for selective COX-2 inhibitors. In silico molecular docking studies coupled with molecular dynamic simulation has been done to rationalize the time-evolved mode of interaction of selected inhibitor inside the active pockets of target COX-2. The binding orientations and binding energy results also showed the selectivity of compounds towards COX-2. Physicochemical properties, pharmacokinetic profile, lipophilicity, water solubility, drug metabolism, drug-likeness properties, and medicinal chemistry of the synthesized isoxazole derivatives were assessed. The SwissADME (absorption, distribution, metabolism, and excretion) database was used to assess the physicochemical properties and drug-likeness properties of the synthesized isoxazole derivatives. All the compounds were shown high GI absorption except Compound 7 ( C7 ). Compound 1 ( C1 ) and Compound 2 ( C2 ) were found to cross the blood-brain barrier (BBB). Lipinski's rule of five is not violated by any of the ten synthesized isoxazole derivatives. It was predicted with the SwissADME database that C2 , C5 , C6 , C7 , and C8 are potent inhibitors of cytochrome (CYP) subtype CYP-2C19. A subtype of CYP-2C9 was inhibited by C4 and C7 . The medicinal chemistry of all the compounds C1 - C10 showed no PAIN (Pan assay interference compounds) alerts. The improved gastrointestinal (GI) absorption and BBB permeability of C1 and C2 can provide a future prospective for new researchers in the medicinal field to investigate the compounds for the management of chronic diseases. The synthesized isoxazole compounds showed excellent in vitro COX-1/2 enzymes anti-inflammatory investigations, in silico studies, good physicochemical properties, and improved pharmacokinetic profile which will be further investigated via in vivo anti-inflammatory activities. Moreover, to further support our findings of the computational research and in vitro studies, an in-vivo pharmacokinetic profile is suggested in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alam, Khan, Saeed Jan, Rashid, Abusharha and Daglia.)

Neurodegenerative ailments are a diverse set of syndromes distinguished by gradual deterioration of the structure as well as functions of the central nervous system or peripheral nervous system. Alzheimer's disease (AD) and Parkinson's disease (PD) have no cure, common, and are high prevalent neurodegenerative pathologies. In current research, rationally designed thiazolidine-2,4-dione based analogs were synthesized and tested for their inhibition potential against two isoforms of monoamine oxidase (MAO-A / MAO-B). Structure activity relationships were explored. Pyridinyl and thiazolyl hydrazone derivative 43 and 44 with IC 50 value of 0.013 µM and 0.008 µM (selectivity 228 / 226 times) exhibited higher potency than reference drug safinamide. Most active compounds showed BBB penetration in PAMPA in-vitro assay. Except nitro derivative 41, all compounds were non-neurotoxic in the studied concentration. Molecular docking studies supported the in-vitro experimental results and the selectivity by comparing the binding energy values against both MAO-A and MAO-B isoforms. All the results of current research suggest compounds 43 and 44 may serve as promising candidates for further research for treatment of neurodegenerative diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Breast cancer (BCa) is very common malignancy and globally, has become the second leading cause of cancer death among women. For the treatment of BCa, estrogen receptors-alpha (ERα) has proven to be a therapeutic target. In continuation of our previous reported dihydropyrimidine-based pregnenolone derivatives, we modified at C-3 hydroxyl group. Structural architecture of estrogen receptors (ER) with excellent ER binding affinity was used for modification. MTT assay was used to evaluate the synthesized steroidal analogs for their antiproliferative activities against ER-positive MCF-7, ER-negative MDA-MB-231 (ER - ) breast cancer cells and non-cancerous HEK-293 cells. Structure activity relationship (SAR) studies revealed that diethanolamine containing pregnenolone derivatives showed significant cytotoxicity against ER + MCF-7 and also showed good binding affinity with ERα and are relatively safe against HEK-293 cell model. Docking studies demonstrated that high binding affinity of diethanolamine analogs is due to their binding interaction with key amino acid residues present in the binding site of Erα., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Alzheimer's disease is the most common progressive neurodegenerative mental disorder associated with loss of memory, decline in cognitive function, and dysfunction of language. The prominent pathogenic causes of this disease involve deposition of amyloid-β plaques, acetylcholine neurotransmitter deficiency, and accumulation of neurofibrillary tangles. There are multiple pathways that have been targeted to treat this disease. The inhibition of the intracellular cyclic AMP regulator phosphodiesterase IV causes the increase in CAMP levels that play an important role in the memory formation process. Organometallic chemistry works in a different way in treating pharmacological disorders. In the field of medicinal chemistry and pharmaceuticals, zinc-based amide carboxylates have been shown to be a preferred pharmacophore. The purpose of this research work was to investigate the potential of zinc amide carboxylates in inhibition of phosphodiesterase IV for the Alzheimer's disease management. Swiss Albino mice under controlled conditions were divided into seven groups with 10 mice each. Group I was injected with carboxymethylcellulose (CMC) at 1 mL/100 g dose, group II was injected with Streptozotocin (STZ) at 3 mg/kg dose, group III was injected with Piracetam acting as a standard drug at 200 mg/kg dosage, while groups IV-VII were injected with a zinc scaffold at the dose regimen of 10, 20, 40, and 80 mg/kg through intraperitoneal injection. All groups except group I were injected with Streptozotocin on the first day and third day of treatment at the dose of 3 mg/kg through an intracerebroventricular route to induce Alzheimer's disease. Afterward, respective treatment was continued for all groups for 23 days. In between the treatment regimen, groups were analyzed for memory and learning improvement through various behavioral tests such as open field, elevated plus maze, Morris water maze, and passive avoidance tests. At the end of the study, different biochemical markers in the brain were estimated like neurotransmitters (dopamine, serotonin and adrenaline), oxidative stress markers (superoxide dismutase, glutathione, and catalase), acetylcholinesterase (AchE), tau proteins, and amyloid-β levels. A PCR study was also performed. Results showed that the LD 50 of the zinc scaffold is greater than 2000 mg/kg. Research indicated that the zinc scaffold has the potential to improve the memory impairment and learning behavior in Alzheimer's disease animal models in a dose-dependent manner. At the dose of 80 mg/kg, a maximum response was observed for the zinc scaffold. Maximum reduction in the acetylcholinesterase enzyme was observed at 80 mg/kg dose, which was further strengthened and verified by the PCR study. Oxidative stress was restored by the zinc scaffold due to the significant activation of the endogenous antioxidant enzymes. This research ended up with the conclusion that the zinc-based amide carboxylate scaffold has the potential to improve behavioral disturbances and vary the biochemical markers in the brain., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The objective of the current study was to evaluate the phytochemical and pharmacological potential of the Cornus macrophylla . C. macrophylla belongs to the family Cornaceae. It is locally known as khadang and is used for the treatment of different diseases such as analgesic, tonic, diuretic, malaria, inflammation, allergy, infections, cancer, diabetes, and lipid peroxidative. The crude extract and different fractions of C. macrophyll were evaluated by gas chromatography and mass spectroscopy (GC-MS), which identified the most potent bioactive phytochemicals. The antioxidant ability of C. macrophylla was studied by 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) and 1,1 diphenyl-2-picryl-hydrazyl (DPPH) methods. The crude and subsequent fractions of the C. macrophylla were also tested against anti-inflammatory enzymes using COX-2 (Cyclooxygenase-2) and 5-LOX (5-lipoxygenase) assays. The molecular docking was carried out using molecular operating environment (MOE) software. The GC-MS study of C. macrophylla confirmed forty-eight compounds in ethyl acetate (Et.AC) fraction and revealed that the Et.AC fraction was the most active fraction. The antioxidant ability of the Et.AC fraction showed an IC 50 values of 09.54 μg/mL and 7.8 μg/mL against ABTS and DPPH assay respectively. Among all the fractions of C. macrophylla , Et.AC showed excellent activity against COX-2 and 5-LOX enzyme. The observed IC 50 values were 93.35 μg/mL against COX-2 and 75.64 μg/mL for 5-LOX respectively. Molecular docking studies supported these in vitro results and confirmed the anti-inflammatory potential of C. macrophylla. C. macrophylla has promising potential as a source for the development of new drugs against inflammation in the future.

Due to a lack of therapeutic options for the pathological condition of leishmaniasis, which is characterized by polymorphic lesions and skin surface infections, Leishmania genus parasites damaged dermis and mucosa. There was a need to synthesize and characterize some new complexes. This study evaluated the biological activities preferably anti-Leishmanial activity of organotin (IV) containing sulphonyl hydrazide derivatives. A series of six new organotin (IV) complexes 1-6 labeled as R2SnL2; R = Methyl (1), Butyl (2), Phenyl (3) and R3SnL; R = Methyl (4), Butyl (5), Phenyl (6) has been synthesized as reflux method derived from N'- (2,4-dinitrophenyl)-4-methylphenylsulfonylhydrazide (L). All compounds were characterized through FT-IR, 1HNMR, 13CNMR, and elemental analysis. Structural analysis confirms the formation of six complexes (1-6). All derivatives have been screened for their pharmacological activities. Interestingly, compound 1 showed promising activity against leishmania promastigotes with low cytotoxicity. All results were further elaborated through docking studies performed on leishmania donovoni synthetase PDB: ID 3QW3 that acts as an essential building block for the viability of Leishmania promastigotes. This research effectively synthesized sulphonyl hydrazide ligand and its six new organotin (IV) derivatives, which were tested for biological properties such as antibacterial, anti-fungal, anti-oxidant, and ideally anti-leishmanial activity and cytotoxicity. Studies have confirmed that these compounds have the potency to be a good candidate against leishmaniasis. Computational studies were carried out to recognize the binding affinities for leishmania donovoni synthetase.Communicated by Ramaswamy H. Sarma.

To obtain a multipotent framework that can target simultaneously COX-2, 5-LOX, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) to treat neuroinflammation, a series of derivatives containing pyrimidine and pyrrolidine cores were rationally synthesized and evaluated. Pyrazoline-pyrimidine hybrid ( 23g ), (3-acetylcoumarin derivative of pyrrolidin-1-yl)benzenesulfonamide ( 27 ), and tacrine derivatives of (pyrrolidin-1-yl)benzenesulfonamide ( 31 , 38 ) displayed excellent in vitro COX-2 inhibition having IC 50 value in the nanomolar range. Tacrine-pyrrolidine hybrids 36 and 38 , and tacrine-pyrimidine hybrid ( 46 ) emerged as the most potent ee AChE inhibitors with IC 50 values of 23, 16, and 2 nM, respectively. However, compounds 27 , 31 , and 38 possessed excellent simultaneous and balanced inhibitory activity against all of the four tested targets and thus emerged as optimal multipotent hybrid compounds among all of the synthesized series of the compounds. In the ex vivo , transgenic animal models treated with compounds 36 and 46 displayed a significant decline in both AChE and BChE potentials in the hippocampus and cortical tissues. In anti-inflammatory activities, animals treated with compounds 36 and 46 displayed a significant % inhibition of edema induced by carrageenan and arachidonic acid. Biochemical analysis and histopathological examination of mice liver indicate that tacrine derivatives are devoid of hepatotoxicity and neurotoxicity against SH-SY5Y neuroblastoma cell lines. In vivo acute toxicity study showed the safety of synthesized compounds up to 1000 mg/kg dose. The inhibitory manner of interaction of these potent drugs on all of the studied in vitro targets was confirmed by molecular docking investigations.