Synthesis and Ameliorative Effect of Isatin–Mesalamine Conjugates on Acetic Acid‐induced Colitis in Rats

A series of new isatin–mesalamine conjugates ( 9a – g ) were synthesized via conjugation of isatin ( 3a ) and its derivatives ( 3b – 3d , 4 , 5 , and 6 ) with mesalamine ( 7 ) by using chloroacetyl chloride as a bifunctional linker. Compounds 3a – 3d were prepared by employing Sandmeyer reaction. Compounds 4 , 5 , and 6 were obtained from isatin ( 3a ) via previously reported methods. The synthesized compounds were characterized by IR, mass, ¹H NMR, and ¹³C NMR spectral techniques. Synthesized compounds ( 3a – d , 4 , 5 , 6 , and 9a – g ) were evaluated for in vitro antioxidant activity by DPPH assay method using ascorbic acid as standard. Hybrids 9b (IC₅₀ = 368.6 ± 3.5 μM) and 9f (IC₅₀ = 335.1 ± 2.9 μM) showed better antioxidant activity than its parent compounds such as 3a (IC₅₀ = 556.8 ± 2.9 μM), 5 (IC₅₀ = 511.9 ± 3.6 μM), and 7 (IC₅₀ = 768.9 ± 2.7 μM). Acetic acid‐induced ulcerative colitis in rat model was chosen to examine the antioxidant potential of the synthesized hybrids ( 9b and 9f ) in the amelioration of ulcerative colitis. Colonic myeloperoxidase and malondialdehyde enzymes were used as biomarkers of anti‐ulcerative colitis activity. In the present study, hybrids 9b and 9f reduced the levels of colonic myeloperoxidase and malondialdehyde enzymes significantly (p < 0.05) when compared with control (colitic), at a dose (0.03 mM/12.5 mg/kg b.w. p.o.) (50%) less than that of its parent moieties mesalamine (0.16 mM/25 mg/kg) and isatin (0.16 mM/25 mg/kg). Thus, the molecular hybridization was proved to be significant in enhancing the activity of hybrids 9b and 9f by reducing the dose.     

Synthesis and Anti‐proliferative Activity of Novel Polysubstitued Indazole Derivatives

A simple and efficient process is developed for the synthesis of new N‐(1‐alkyl‐3‐chloro‐4‐ethoxy‐1H‐indazol‐5‐yl)‐arylsulfonamides 4a – d and N‐(1‐alkyl‐3‐chloro‐1H‐indazol‐5‐yl)‐arylsulfonamides 5a – d through the reduction of 1‐alkyl‐3‐chloro‐5‐nitroindazoles 2a , b with SnCl₂ in ethanol followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. All the newly synthesized compounds have been characterized by elemental analysis and spectroscopic data. Some compounds were tested for their in vitro antiproliferative activities against two selected human cancer cell lines A2780 and A549. Among all of these derivatives, compound 5d showed the most potent antiproliferative activity against A2780 (IC₅₀ = 5.47 ± 1.45 μM) and A549 (IC₅₀ = 7.73 ± 1.66 μM) cell lines.     

Design,Synthesis, and Anticancer Activities of Benzofuran–Isatin Hybrids Tethered by Pentylene and Hexylene

Fourteen benzofuran–isatin hybrids 6a – f and 7a – h tethered via alkyl linker (pentylene and hexylene) were designed and synthesized, and hybrids 6c – f and 7a – h were screened for their in vitro anticancer activity against various human cancer cell lines. The majority of the hybrids were active against the tested cancer cells, and the most active hybrids 7g (half maximal inhibitory concentration/IC₅₀: 77.2–88.9 μM) and 7h (IC₅₀: 65.4–89.7 μM), which possessed broad spectrum anticancer activity were as potent as the reference vorinostat (IC₅₀: 64.2–>100 μM) against all tested cancer cell lines, could act as leads for further investigations. The structure–activity relationship is also discussed, and the enriched structure–activity relationship may afford useful information for further rational design of the candidates with higher activity.     

Design,Synthesis, and Pharmacological Assay of Novel Compounds Based on Pyridazine Moiety as Potential Antitumor Agents

In an endeavor to develop antitumor agents, we made a credible survey regarding synthesis, structure, and pharmacological assay of novel pyridazine derivatives, so that 2‐((6‐(4‐chloro‐3‐methylphenyl)pyridazin‐3‐yl)oxy)acetohydrazide 3 was utilized as scaffold to build novel compounds 4 – 19 by reaction with various electrophilic reagents, followed by determination and explanation atropisomerism phenomena and tauomerism ratio such as keto‐enol and lactam–lactim tautomers for some synthesized compounds. In vitro, these compounds were screened for antitumor efficacy versus two cell lines, namely, hepatocellular carcinoma and mammary gland breast cancer, by using MTT assay. Among the examined compounds, compound 16 was exhibited promising potent activity (IC₅₀ = 8.67 ± 0.7 μM) versus HepG2 cell line. Meanwhile, compounds 3 and 16 were manifested the very highest efficacy (IC₅₀ = 5.68 ± 0.6 and 9.41 ± 0.9 μM) versus MCF‐7 cell line.     

Functionalization of Quinazolin‐4‐ones Part 3: Synthesis,Structures Elucidation,DNA‐PK,PI3K,and Cytotoxicity of Novel 8‐Aryl‐2‐morpholino‐quinazolin‐4‐ones

A series of novel 8‐aryl‐2‐morpholino quinazolines ( 11a – n , 12a – d , 14a – f , and 15 ) were synthesized from the precursor 2‐thioxo quinazolin‐4‐ones 8 . The 8‐aryl‐2‐morpholino quinazolines compounds were assayed for DNA‐PK and PI3K. All compounds showed low DNA‐PK % inhibition activity at 10 μM compound concertation, and the most active was 8‐(dibenzo[b,d]thiophen‐4‐yl) 12d with 38% inhibition. Similar pattern of PI3K α, β, γ, and δ isoforms inhibition activity at 10 μM were observed. The most active isoform was PI3K δ of 41% inhibition for 8‐(dibenzo[b,d]furan‐4‐yl) compound 11 . Most compounds were less active than expected in spite of the strong structural resemblance to known inhibitors ( NU7441 , 3 , 4 , and 6 ). Loss of activity could be attributed to the tautomerization to the aromatic enol (4‐OH), which could specify that the important functional group for the activity is the 4‐carbonyl (C=O) group. Alternatively, the aromatization of the pyrimidine heterocyclic ring could alter the conformation, and thus binding site, of the 2‐morpholine ring, which could reduce the compound‐receptor hydrogen bonding to the morpholine 4‐oxygen. Selected compounds displayed appreciable cytotoxicity with 6‐chloro‐8‐(dibenzo[b,d]thiophen‐4‐yl)‐2‐morpholinoquinazolin‐4(1H)‐one 11j exhibiting the greatest activity with an IC₅₀ of 9.95 μM. Therefore, the mechanism of the cytotoxicity of compound 11j were not through DNA‐PK or PI3K inhibition activity.     

Synthesis,in vitro urease inhibitory activity and molecular docking of 3,5‐disubstituted thiadiazine‐2‐thiones

A series of 3,5‐disubstituted‐tetrahydro‐thiadiazine‐2‐thione ( 1 ‐ 16 ) have been synthesized, characterized by elemental analysis, infrared (IR), UV‐visible, ¹H NMR, ¹³C NMR, and MS spectroscopic techniques, and screened against jack bean urease. Among 16 compounds, compounds ( 1 ), ( 2 ), ( 3 ), ( 4 ), ( 6 ), ( 7 ), and ( 9 ) demonstrated excellent urease inhibitory activity with IC₅₀ values (9.8 ± 0.5, 11.0 ± 0.6, 16.0 ± 1.5, 17.2 ± 0.5, 15.4 ± 0.5, 19.7 ± 0.4, and 15.8 ± 0.2μM), respectively, even better than the standard thiourea (IC₅₀ = 21 ± 0.01μM). However, compound ( 8 ) shows an almost same level of inhibition (IC₅₀ = 22.9 ± 0.3μM), as like standard. In this work, we reported for the first time urease inhibitory activity of thiadiazine thiones and its molecular docking studies.     

Synthesis,Biological Evaluation,and Molecular Docking Studies of Novel Pyrazolo[3,4‐d]pyrimidines as Potential Telomerase Inhibitors

Series of novel pyrazolo[3,4‐d]pyrimidines as potential telomerase inhibitors were synthesized. Results of the antitumor assay indicated that compounds 4b , 5a – b , 13b , c , and 14a , b exhibited the most potent activity (IC₅₀ from 39 to 43 μM) against Ehrlich ascites carcinoma cells (EAC). Also, the newly synthesized compounds were examined for telomerase inhibition by the known a TRAP assay. The results showed that compound 13c has remarkable inhibition activity with IC₅₀ value of 30 μM. On the other hand, computational studies were performed to the titled compounds to get insight in their degree of recognition with the conserved amino acids of the telomerase enzyme active site (code: 3DU6) as promising lead in the cancer cure era.     

Regioselective Reactions,Spectroscopic Characterization,and Cytotoxic Evaluation of Spiro‐pyrrolidine Thiophene

Spiro‐oxo‐indole/pyrrolidine‐thiophene base possessed significant pharmacological activity. The [3 + 2] cycloaddition reactions of thia‐methine ylide respected through multi‐component reaction affording regioselective and stereoselective spiroindoline‐3,2′‐tetrahydrothiophene derivative 3 . Reaction of such compound with different electrophilic and nucleophilic reagents afforded bioactive heterocyclic compounds 4 – 16 . Biological evaluation showed that these synthesized spiro‐pyrrolidine exhibited moderate to good cytotoxic activity. Among them, compounds 7 and 14 displayed the best cytotoxic activity against MCF‐7 and Wl‐38 cells with the IC₅₀ values of 7.02 ± 0.6 and 8.97 ± 0.9 μm (very strong), respectively. Compounds 4 , 5 , and 12 exhibited strong cytotoxicity's with IC₅₀ 16.28 ± 1.7, 11.16 ± 1.1, and 19.14 ± 1.7 μm, respectively, against MCF‐7 mammary gland cell line. All compound structures were supported by spectroscopic data and elemental analysis.     

Synthesis and biological evaluation of some 1,3-benzoxazol-2(3H)-one hybrid molecules as potential antioxidant and urease inhibitors

A new series of 1,3-benzoxazol-2(3H)-one hybrid compounds, including coumarin, isatin 1,3,4-triazole and 1,3,4-thiadiazole moieties, were synthesized and biologically evaluated for their antioxidant capacities and anti-urease properties. The synthesized benzoxazole-coumarin ( 6a–e ) and benzoxazole-isatin ( 10a–c ) hybrids showed remarkable urease inhibitory activities with IC₅₀ (μM), ranging from 0.0306 ± 0.0030 to 0.0402 ± 0.0030, while IC₅₀ of standard thiourea is 0.5027 ± 0.0293. The synthesized benzoxazole-triazole ( 8a–c ) and benzoxazole-thiadiazole ( 9a–c ) hybrids showed similar urease inhibitory activities with IC₅₀ (μM), ranging from 0.3861 ± 0.0379 to 0.5126 ± 0.0345. The antioxidant activity of the synthesized compounds was evaluated for their antioxidant activities, such as reducing power and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt) radical scavenging. The results of ABTS radical scavenging activities of some of the synthesized molecules showed higher activities than standard Trolox, SC₅₀ (μM) = 213.04 ± 18.12. One benzoxazole-coumarin ( 6f ), two benzoxazole-isothiocyanate ( 7b, 7c ), and two benzoxazole-triazole ( 8b, 8c ) derivatives showed higher activities (SC₅₀ (μM) values, 82.07 ± 10.34, 120.19 ± 7.30, 104.58 ± 10.55, 153.26 ± 7.14, and 144.82 ± 10.68, respectively) than standard Trolox, (SC₅₀ (μM) = 213.04 ± 18.12).     

Anticancer activity of Ophiobolin A,isolated from the endophytic fungus Bipolaris setariae

The present work describes the anticancer activity of Ophiobolin A isolated from the endophytic fungus Bipolaris setariae. Ophiobolin A was isolated using preparative HPLC and its structure was confirmed by HRMS, ¹H NMR, ¹³C NMR, COSY, DEPT, HSQC and HMBC. It inhibited solid and haematological cancer cell proliferation with IC₅₀ of 0.4–4.3 μM. In comparison, IC₅₀ against normal cells was 20.9 μM. It was found to inhibit the phosphorylation of S6 (IC₅₀ = 1.9 ± 0.2 μM), ERK (IC₅₀ = 0.28 ± 0.02 μM) and RB (IC₅₀ = 1.42 ± 0.1 μM), the effector proteins of PI3K/mTOR, Ras/Raf/ERK and CDK/RB pathways, respectively. It induced apoptosis and inhibited cell cycle progression in MDA-MB-231 cancer cells with concomitant inhibition of signalling proteins. Thus, this study reveals that anticancer activity of Ophiobolin A is associated with simultaneous inhibition of multiple oncogenic signalling pathways namely PI3K/mTOR, Ras/Raf/ERK and CDK/RB.     

Design,synthesis and biological evaluation of isoxazole-naphthalene derivatives as anti-tubulin agents

In this study, a novel series of isoxazole-naphthalene derivatives as tubulin polymerization inhibitors were designed, synthesized and evaluated for their anti-proliferative activities against human breast cancer cell line MCF-7. Most of the synthesized compounds exhibited moderate to potent antiproliferative activity (IC₅₀ < 10.0 μM), as compared to cisplatin (15.24 ± 1.27 μM). Among them, compound 5j containing 4-ethoxy substitution at phenyl ring was found to be the most active compound with IC₅₀ value of 1.23 ± 0.16 μM. Mechanistic studies revealed that compound 5j arrested cell cycle at G2/M phase and induces apoptosis. Furthermore, in vitro tubulin polymerization assay showed that compound 5j displayed better inhibition activity on tubulin polymerization (IC₅₀ = 3.4 μM) than colchicine (IC₅₀ = 7.5 μM). Molecular docking study also revealed that compound 5j binds to the colchicine binding site of tubulin.     

Synthesis,Structural, Biological Evaluation,Molecular Docking and DFT Studies of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) Complexes bearing Heterocyclic Thiosemicarbazone ligand

A new ligand, 2‐aminonicotinaldehyde N‐methyl thiosemicarbazone (ANMTSC) and its metal complexes [Co(II) ( 1 ); Ni(II) ( 2 ); Cu(II) ( 3 ); Zn(II) ( 4 ); Cd(II) ( 5 ) or Hg(II) ( 6 )] were synthesized. The compounds were characterized by analytical methods and various spectroscopic (infrared, magnetic, thermal, ¹H, ¹³C NMR, electronic and ESR) tools. The structure of ANMTSC ligand was confirmed by single crystal X‐ray diffraction study. The spectral data of metal complexes indicate that the ligand acts as mononegative, bidentate coordination through imine nitrogen (N) and thiocarbonyl sulphur (S^?) atoms. The proposed geometries for complexes were octahedral ( 1 – 2 ), distorted octahedral ( 3 ) and tetrahedral ( 4 – 6 ). Computational details of theoretical calculations (DFT) of complexes have been discussed. The compounds were subjected to antimicrobial, antioxidant, antidiabetic, anticancer, ROS, studies and EGFR targeting molecular docking analysis. Complex 5 has shown excellent antibacterial activity and the complexes 2 and 5 have shown good antifungal activity. The complexes 1 and 4 displayed good antioxidant property with IC₅₀ values of 11.17 ± 1.92 μM and 10.79 ± 1.85 μM, respectively compared to standard. In addition, in vitro anticancer activity of the compounds was investigated against HeLa, MCF‐7, A549, IMR‐32 and HEK 293 cell lines. Among all the compounds, complex 4 was more effective against HeLa (IC₅₀ = 10.28 ± 0.69 μM), MCF‐7 (IC₅₀ = 9.80 ± 0.83 μM), A549 (IC₅₀ = 11.08 ± 0.57 μM) and IMR‐32 (10.41 ± 0.60 μM) exhibited superior anticancer activity [IC₅₀ = 9.80 ± 0.83 ( 4 ) and 9.91 ± 0.37 μM ( 1 )] against MCF‐7 compared with other complexes.     

Synthesis,Antimicrobial, and Anticancer Activities of a New Series of Thieno[2,3‐d] Pyrimidine Derivatives

A new series from thieno[2,3‐d] pyrimidine derivatives have been synthesized based on 2‐(ethylmercapto)‐4‐mercapto‐6‐phenyl‐5‐pyrimidine carbonitrile, these compounds used in the synthesis of many pyrimidothienopyrimidine derivatives and triazolo[1″,5″:1″,6″]pyrimido[4′,5′:4,5]thieno[2,3‐d] pyrimidine derivatives. The chemical composition of these compounds was confirmed by ¹H NMR, ¹³C NMR, and MS techniques. Some of the synthesized compounds were screened for their antimicrobial and anticancer agent. Compound ( 9b ) showed strong effect on Aspergillus Fumigatus (RCMB 2568), Candida albicans (RCMB 05036), Saphylococcus aureus (RCMB 010010), Bacillis subtilis (RCMB 010067), Salmonella sp. (RCMB 010043), and Escherichia coli (RCMB 010052). Compounds ( 2 ) and ( 5a – k ) were evaluated for their IC₅₀ values against two cancer cell lines (MCF‐7 and HeLa cells) in the presence of Paclitaxel as reference material. Compound ( 5g ) showed the highest cytotoxicity against MCF‐7 (IC₅₀ values about 18.87 ± 0.2 μg/mL) cells compared with Paclitaxel (IC₅₀ values about 40.37 ± 1.7 μg/mL). Also, compound ( 5d ) showed the highest cytotoxicity against HeLa (IC₅₀ values about 40.74 ± 1.7 μg/mL) cells compared with Paclitaxel (IC₅₀ values about 45.78 ± 0.8 μg/mL).     

Indolyl Linked Meta‐Substituted Benzylidenes as Novel Ligands: Synthesis,Biological Evaluation,and Molecular Docking Studies

Synthesis of indolyl linked benzylidene based meta‐substituted phenyl containing thiazolidinediones ( 4a – b ), rhodanine ( 5a – b ), and 1,3‐dicarbonyl based acyclic analogs of isoxazolidinediones ( 6a – 7b ) in an effort to develop novel α‐glucosidase inhibitors in the management of hyperglycemia for the treatment of type 2 diabetes is reported. The structure of all the novel synthesized compounds was confirmed through the spectral studies (LC–MS, ¹H‐NMR, ¹³C‐NMR, and FTIR). Comparative evaluation of these compounds revealed that the compound 5b showed maximum inhibitory potential against α‐amylase and α‐glucosidase giving an IC₅₀ value of 0.28 ± 0.01 μM. Furthermore, binding affinities in terms of G score values and hydrogen bond interactions between all the synthesized compounds and the AA residues in the active site of the protein (PDB code: 3TOP) to that of Acarbose (standard drug) were explored with the help of molecular docking studies. Compound 5b was considered as promising candidate of this series.     

Design,Synthesis, and Biological Evaluation of 2‐(4‐Aminophenyl)benzothiazole Analogues as Antiproliferative Agents

A series of 28 novel 2‐(4‐aminophenyl)benzothiazole analogues have been synthesized and characterized using various analytical techniques like ¹H NMR, ¹³C NMR, electrospray ionization mass spectrometry, and IR and bioevaluated for their antiproliferative activity over a group of three human cancer cell lines, namely, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MDA‐MB‐231), using sulforhodamine B assay method. Few synthesized molecules ( 5a , 5c , 5d , 5f , 7b , and 7j ) displayed effective growth inhibition (GI₅₀) activity against the tested human cancer cell lines at lower micromolar concentration (GI₅₀) values in the range 0.2–1.7 μM. Noticeably, compound 7b exhibited reasonable activity in all three cancer cell lines in the GI₅₀ range 0.55–1.2 μM. Further, when 7b was screened for tubulin polymerization inhibition, it exhibited more than 55% inhibition at concentration of 5.0 μM. The molecular docking simulations supported the molecular interactions of the derivatives with the targeted receptor. These derivatives may serve as lead structures for development of potential anticancer drug candidates, and 7b might act as a potential microtubule polymerization inhibitor.     

Synthesis of Novel 1,2,4‐Triazole‐3‐thione Derivatives as Influenza Neuraminidase Inhibitors

A series of 1,2,4‐triazole‐3‐thione derivatives ( 6a – 6t ) were synthesized and evaluated against influenza viruses (H1N1) neuraminidase (NA) in vitro. Eighteen compounds exhibited inhibitory potency with IC₅₀ values ranging from 14.68 ± 0.49 to 39.85 ± 4.23 μg/mL. Among them, compounds 6e and 6h showed significant inhibitory activity with IC₅₀ values of 14.97 ± 0.70 and 14.68 ± 0.49 μg/mL, respectively. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction between active compounds and NA.     

Molecular Substantiation and Drug Efficacy of Relatively High Molecular Weight S‐BINOLs; Appraised as Breast Cancer Medication and PI3Kinase Inhibitors

Relatively high molecular weight S‐BINOLs with substituted functional groups were synthesized, and structures were elucidated by FTIR, ¹H nuclear magnetic resonance, ¹³C nuclear magnetic resonance, and HRMS. As a preliminary step, the compounds were docked into the active site of phosphoinositide3‐kinase (PI3Kinase) (Protein Data Bank ID: 2IUG) that is a crucial regulator of apoptosis or programmed cell death. To ensure the PI3Kinase inhibition, because it was predicted as the most suitable bioactivity of these compounds, a competitive ELISA PI3Kinase inhibition study was carried out. Compounds 3 , 4a , 4b , and 6 were assessed for cytotoxicity/antiproliferative effects on MCF‐7 (breast cancer) and HCT116 (colon cancer) cell lines. In the docking studies, excellent binding affinities of 3 , 4a , 4b , and 6 (−11.36, −14.52, −14.86, and −21.76 kcal/mol, respectively) and the inhibitory constants (ki) (4.75 nM, 81.64 pM, 78.23 pM, and 14.24 pM, respectively) encouraged us to carry out anticancer studies further. Excellent inhibitory values were obtained in the range of 82–90% relative activity and IC₅₀ range of 5–12 nM. In the cytotoxicity, the relative inhibition activity was remarkably found high in MCF‐7 cell lines as 89.14% ( 6 ), 82.18% ( 4b ), 80.46% ( 3 ), and 74.78% ( 4a ) with the IC₅₀ range of 0.02–0.18 μM. No compounds were found inactive for the proposed activity in this study. The Structure Activity Relationship studies prove that compounds 3 , 4a , 4b , and 6 are specific PI3Kinase inhibitors with the competence to cure breast cancers.     

Structure‐cytotoxicity relationship for apoptotic inducers organotin(IV) derivatives of mandelic acid and L‐proline and their mixed ligand complexes having enhanced cytotoxicity

Structure‐cytotoxicity relationship of di?/tri‐organotin(IV) derivatives of mandelic acid ( 1 – 4 ), L‐proline ( 5 – 7, 15, 16 ), and mixed ligand complexes of latter with 1,10‐phenanthroline ( 8 – 14 ) investigated on the basis of MTT assay against human cancer cell lines, viz. MCF‐7 (mammary cancer), HepG2 (liver cancer) and PC‐3 (prostate cancer) in vitro indicated that all complexes except methyl‐ and octyl‐ analogues displayed potential cytotoxicity. The most active one is dibutyltin(IV) mandelate ( 2 ) exhibiting IC₅₀ 2.03 ± 0.40, 0.98 ± 0.23 and 3.86 ± 1.68 μM against MCF‐7, HepG2 and PC‐3, respectively, which is ≈ 15 and 2.5 times against MCF‐7, 20 and 5 times against HepG2 and 5 and ≈ 3 times against PC‐3 more cytotoxic than cis‐platin and 5‐fluorouracil, respectively. Diorganotin(IV) derivatives of mandelic acid are more cytotoxic than triorganotin analogues. Organotin(IV) derivatives of L‐proline (except Bu₃Sn(Pro) 16 ) are less cytotoxic than those of mandelic acid but their cytotoxicity is enhanced by complexion with 1,10‐phenanthroline. This may be due to the structural planarity and extended π system of 1,10‐phenanthroline which facilitates their transportation across the cell membrane and enhances the possibility of DNA intercalation over the planar L‐proline ring, and eventually, their DNA binding affinity so as to interfere with the cellular functions of DNA leading to apoptosis. Various biophysical experiments such as DNA fragmentation, acridine orange and comet assays, and flow cytometry assay using annexin V–fluorescein isothiocyanate (FITC) and propidium iodide (PI) have been carried out in order to ascertain their mode of action. The observed results indicated that the major cause of cancer cell death is apoptosis, but a minor role played by necrosis cannot be excluded. It is concluded on the basis of the observed results that the nature and number of organic groups bonded to tin as well as the nature of counter anions play an important role in determining the cytotoxicity of organotin(IV) compounds.     

Identification of novel diclofenac acid and naproxen bearing hydrazones as 15-LOX inhibitors: Design,synthesis, in vitro evaluation,cytotoxicity, and in silico studies

Inflammation is the immune system's adaptive response to tissue dysfunction or homeostatic imbalance, inducing fever, pain, physiological and biochemical changes via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. NSAIDs (non-steroidal anti-inflammatory drugs), such as diclofenac acid and naproxen, are the most common inhibitors of the COX pathway. These drugs, however, are currently being studied as LOX inhibitors as well. Therefore, in the present study, a novel series of diclofenac acid and naproxen-bearing hydrazones 7(a-r) were designed, synthesized, and characterized by different spectroscopic methods like ¹H NMR, ¹³C NMR, IR and HRMS (EI) analysis. All these synthesized compounds were evaluated for their in vitro inhibitory potential against the Soybean 15-lipoxygenase (15-LOX) enzyme. These compounds exhibited varying degrees of inhibitory potential ranging from IC₅₀ 4.61 ± 3.21 μM to 193.62 ± 4.68 μM in comparison to standard inhibitors quercetin (IC₅₀ 4.84 ± 6.43 μM) and baicalein (IC₅₀ 22.46 ± 1.32 μM). The most potent compounds in the series were compounds 7c (IC₅₀ 4.61 ± 3.21 μM), and 7f (IC₅₀ 6.64 ± 4.31 μM). These compounds were found least cytotoxic and showed 96.42 ± 1.3 % and 94.87 ± 1.6 % viability to cells at 0.25 mM concentration respectively. ADME and in silico studies supported the drug-likeness and binding studies of the molecules with the target enzyme.