Anticancer properties of complexes derived from bidentate ligands.

Cancer is the abnormal division and multiplication of cells in an organ or tissue. It is the second leading cause of death globally. There are various types of cancer such as prostate, breast, colon, lung, stomach, liver, skin, and many others depending on the tissue or organ where the abnormal growth originates. Despite the huge investment in the development of anticancer agents, the transition of research to medications that improve substantially the treatment of cancer is less than 10%. Cisplatin and its analogs are ubiquitous metal-based anticancer agents notable for the treatment of various cancerous cells and tumors but unfortunately accompanied by large toxicities due to low selectivity between cancerous and normal cells. The improved toxicity profile of cisplatin analogs bearing bidentate ligands has motivated the synthesis of vast metal complexes of bidentate ligands. Complexes derived from bidentate ligands such as ß-diketones, diolefins, benzimidazoles and dithiocarbamates have been reported to possess 20 to 15,600-fold better anticancer activity, when tested on cell lines, than some known antitumor drugs currently on the market, e.g. cisplatin, oxaliplatin, carboplatin, doxorubicin, and 5-fluorouracil. This work discusses the anticancer properties of various metal complexes derived from bidentate ligands, for possible application in chemotherapy. The results discussed were evaluated by the IC50 values as obtained from cell line tests on various metal-bidentate complexes. The structure-activity relationship study of the complexes discussed, revealed that hydrophobicity is a key factor that influences anticancer properties of molecules.

Synthesis, Structure, Hirshfeld Surface Analysis, Non-Covalent Interaction, and In Silico Studies of 4-Hydroxy-1-[(4-Nitrophenyl)Sulfonyl]Pyrrolidine-2-Carboxyllic Acid.

The new compound 4-hydroxy-1-[(4-nitrophenyl)sulfonyl]pyrrolidine-2-carboxyllic acid was obtained by the reaction of 4-hydroxyproline with 4-nitrobenzenesulfonyl chloride. The compound was characterized using single crystal X-ray diffraction studies. Spectroscopic methods including NMR, FTIR, ES-MS, and UV were employed for further structural analysis of the synthesized compound. The title compound was found to have crystallized in an orthorhombic crystal system with space group P212121. The S1-N1 bond length of 1.628 (2) Å was a strong indication of the formation of the title compound. The absence of characteristic downfield 1H NMR peak of pyrrolidine ring and the presence of S-N stretching vibration at 857.82 cm-1 on the FTIR are strong indications for the formation of the sulfonamide. The experimental study was complemented with computations at the B3LYP/6-311G + + (d,p) level of theory to gain more understanding of interactions in the compound at the molecular level. Noncovalent interaction, Hirsfeld surface analysis and interaction energy calculations were employed in the analysis of the supramolecular architecture of the compound. Predicted ADMET parameters, awarded suitable bioavailability credentials, while the molecular docking study indicated that the compound enchants promising inhibition prospects against dihydropteroate synthase, DNA topoisomerase, and SARS-CoV-2 spike. Graphical Abstract: Herein we present the solid state structure, noncovalent interaction and spectroscopic analysis of a prospective bioactive compound 4-hydroxy-1-[(4-nitrophenyl)sulphonyl]pyrrolidine-2-carboxyllic acid. Supplementary Information: The online version contains supplementary material available at 10.1007/s10870-023-00978-0.

Structure and Computational Studies of New Sulfonamide Compound: {(4-nitrophenyl)sulfonyl}tryptophan.

Synthesis of sulfonamide through an indirect method that avoids contamination of the product with no need for purification has been carried out using the indirect process. Here, we report the synthesis of a novel sulfonamide compound, ({4-nitrophenyl}sulfonyl)tryptophan (DNSPA) from 4-nitrobenzenesulphonylchloride and L-tryptophan precursors. The slow evaporation method was used to form single crystals of the named compound from methanolic solution. The compound was characterized by X-ray crystallographic analysis and spectroscopic methods (NMR, IR, mass spectrometry, and UV-vis). The sulfonamide N-H NMR signal at 8.07-8.09 ppm and S-N stretching vibration at 931 cm-1 indicate the formation of the target compound. The compound crystallized in the monoclinic crystal system and P21 space group with four molecules of the compound in the asymmetric unit. Molecular aggregation in the crystal structure revealed a 12-molecule aggregate synthon sustained by O-H⋯O hydrogen bonds and stabilised by N-H⋯O intermolecular contacts. Experimental studies were complemented by DFT calculations at the B3LYP/6-311++G(d,p) level of theory. The computed structural and spectroscopic data are in good agreement with those obtained experimentally. The energies of interactions between the units making up the molecule were calculated. Molecular docking studies showed that DNSPA has a binding energy of -6.37 kcal/mol for E. coli DNA gyrase (5MMN) and -6.35 kcal/mol for COVID-19 main protease (6LU7).

Carbohydrazide Analogues: A Review of Synthesis and Biological Activities.

Carbohydrazides and their Schiff bases are important classes of heterocycles that are not only employed in the area of organic chemistry but also have tremendous applications in physical and inorganic chemistry. A series of potentially bioactive compounds containing carbohydrazide functionality and their hydrazone derivatives have been synthesized and screened for antibacterial, anticancer, antifungal and anti-inflammatory, etc. This brief review discloses some synthetic routes to so many reported carbohydrazides, their Schiff bases, their biological activities, and their structure-activity relationship.

Synthesis and Biological Properties of some New Lead Sulphonamide and Carboxamide Scaffolds Bearing Coumarin Moieties.

Coumarin, sulphonamide, and amide scaffolds exhibit diverse pharmacological features and constitute an important class of therapeutic agents. In this review, we have discussed the synthesis, biological properties, and SAR of coumarins containing sulphonamide or amide group in the last seven years. Many reviews on the therapeutic activities of coumarins, sulphonamides, and amides have been published. Hence the authors focused on coumarin-linked sulphonamide or amide scaffolds. The review provides information on the synthetic route to new coumarins containing sulphonamide or amide groups with improved pharmacological properties.

Biological Activity Evaluation of Some New Benzenesulphonamide Derivatives.

Bacterial resistance to antibiotics has become one of the most challenging problems of infectious disease treatment. Ten new derivatives of benzenesulphonamide bearing carboxamide functionality were synthesized and investigated for their in vivo anti-inflammatory, in vitro anti-microbial and anti-oxidant activities. The base promoted reactions of the appropriate amino acids with substituted benzenesulphonyl chlorides gave the benzene sulphonamides (3a-j) in excellent yields. Palladium mediated amidation of the benzenesulphonamides (3a-j) and butylamine gave the new carboxamides (4a-j) in excellent yield. Compounds 4a and 4c inhibited carrageenan induced rat-paw edema at 94.69, 89.66, and 87.83% each at 1, 2, and 3 h, respectively. In the antimicrobial activity, compound 4d (MIC 6.72 mg/mL) was most potent against E. coli, compound 4h (MIC 6.63 mg/mL) was the most active against S. aureus, compound 4a (MIC 6.67 and 6.45 mg/mL) was most active against P. aeruginosa and S. typhi, respectively, compound 4f (MIC 6.63 mg/mL) was the most active against B. subtilis, compounds 4e and 4h (MIC 6.63 mg/mL) each were the most active against C. albicans, while compound 4e (MIC 6.28 mg/mL) was most active against A. niger. Only compound 4e (IC50 0.3287 mg/mL) had comparable activity with Vitamin C (IC50 0.2090 mg/mL).

New carboxamides bearing benzenesulphonamides: Synthesis, molecular docking and pharmacological properties.

Ten new derivatives of benzenesulphonamide bearing carboxamide functionality were synthesized and investigated for their in vitro antimicrobial, antioxidant and in vivo anti-inflammatory activities. Compound 9d inhibited carrageenan induced rat-paw oedema at 93.81, 88.79 and 86.09% at 1 h, 2 h and 3 h administration respectively. In the antimicrobial activity, compound 9a (6.54, 6.69 and 6.64 mg/mL) was most potent against S. aureus, B. subtilis and C. albicans respectively, compound 9e (6.45 and 6.46 mg/mL) was most active against P. aeruginosa and A. niger respectively while compound 9i (6.24 mg/mL) was most active against E. coli. Only compound 9a (IC50 0.3052 mg/mL) had comparable activity with Vitamin C (IC50 0.2090 mg/mL) in the antioxidant assay.

Synthesis, characterization and in vitro antitrypanosomal activities of new carboxamides bearing quinoline moiety.

The reported toxicities of current antitrypanosomal drugs and the emergence of drug resistant trypanosomes underscore the need for the development of new antitrypanosomal agents. We report herein the synthesis and antitrypanosomal activity of 24 new amide derivatives of 3-aminoquinoline, bearing substituted benzenesulphonamide. Nine of the new derivatives showed comparable antitrypanosomal activities at IC50 range of 1-6 nM (melarsoprol 5 nM). Compound 11n and 11v are more promising antitrypanosomal agents with IC50 1.0 nM than the rest of the reported derivatives. The novel compounds showed satisfactory predicted physico-chemical properties including oral bioavailability, permeability and transport properties.

Novel anti-inflammatory and analgesic agents: synthesis, molecular docking and in vivo studies.

Twelve new derivatives of benzothiazole bearing benzenesulphonamide and carboxamide were synthesised and investigated for their in vivo anti-inflammatory, analgesic and ulcerogenic activities. Molecular docking showed an excellent binding interaction of the synthesised compounds with the receptors, with 17c showing the highest binding energy (-12.50 kcal/mol). Compounds 17c and 17i inhibited carrageenan-induced rat paw oedema at 72, 76, and 80% and 64, 73, and 78% at 1 h, 2 h, and 3 h, respectively. In the analgesic activity experiment, compounds 17c, 17 g, and 17i had ED50 (µM/kg) of 96, 127, and 84 after 0.5 h; 102, 134, and 72 after 1 h and 89, 156, and 69 µM/kg after 2 h, respectively, which were comparable with 156, 72, and 70 µM/kg for celecoxib. The ulcerogenic index of the most active derivatives 17c and 17i were 0.82 and 0.89, respectively, comparable to 0.92 for celecoxib. The physicochemical studies of the new derivatives showed that they will not have oral bioavailability problems.

New carboxamide derivatives bearing benzenesulphonamide as a selective COX-II inhibitor: Design, synthesis and structure-activity relationship.

Sixteen new carboxamide derivatives bearing substituted benzenesulphonamide moiety (7a-p) were synthesized by boric acid mediated amidation of appropriate benzenesulphonamide with 2-amino-4-picoline and tested for anti-inflammatory activity. One compound 7c showed more potent anti-inflammatory activity than celecoxib at 3 h in carrageenan-induced rat paw edema bioassay. Compounds 7g and 7k also showed good anti-inflammatory activity comparable to celecoxib. Compound 7c appeared selectivity index (COX-2/COX-1) better than celecoxib. Compound 7k appeared selectivity index (COX-2/COX-1) a little higher than the half of celecoxib while compound 7g is non-selective for COX-2. The LD50 of compounds 7c, 7g and 7k were comparable to celecoxib.