Growth inhibition area of the compounds 4, 6, 8, and 11 at 10 mg/mL by the agar well diffusion method against Gram-positive, Gram-negative bacteria, and yeast strains
Compound
Zone of inhibition/mm
S. aureus
S. epidermidis
M. smegmatis
P. aeruginosa
S. cerevisiae
C. albicans
4
n.a.
7
n.a.
n.a.
7
n.a.
6
n.a.
n.a.
n.a.
n.a.
8
n.a.
8
6
n.a.
n.a.
n.a.
8
n.a.
11
15
12
n.a.
n.a.
9
n.a.
Positive control
VAN 26
VAN 27
RIF 48
NOR 33
NYS 31
NYS 29
n.a.: not active; NOR: norfloxacin; NYS: nystatin; RIF: rifampicin
The authors declare that they have no conflicts of interest.
Ethical approval
Not applicable.
Consent to participate
Not applicable.
Consent to publication
Not applicable.
Availability of data and materials
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.
Funding
This work was partially supported by the Foundation for Science and Technology (FCT), Portugal, via Strategic Projects [UIDB/00100/2020, UIDP/00100/2020 (CQE), LA/P/0056/2020 (IMS), UIDB/04326/2020, UIDP/04326/2020, LA/P/0101/2020 (CCMAR), UIDB/04539/2020, UIDP/04539/2020, LA/P/0058/2020 (CIBB), UIDB/04567/2020, UIDP/04567/2020 (CBIOS)]. Funds from operational programs CRESC Algarve 2020 and COMPETE 2020 through project EMBRC.PT [ALG-01-0145-FEDER-022121] are object of acknowledgement. LMTF expresses gratitude to FCT for the work contract nº IST-ID/115/2018. ICCC and MM thank FCT for the PhD grants [SFRH/BD/08242/2020, SFRH/BD/146441/2019], respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Superti-Furga G, Cochran J, Crews CM, Frye S, Neubauer G, Prinjha R, et al. Where is the future of drug discovery for cancer?Cell. 2017;168:564–5. [DOI] [PubMed]
Gülçin İ. Antioxidant activity of food constituents: an overview.Arch Toxicol. 2012;86:345–91. [DOI] [PubMed]
Walker B, Barrett S, Polasky S, Galaz V, Folke C, Engström G, et al. Looming global-scale failures and missing institutions.Science. 2009;325:1345–6. [DOI] [PubMed]
D’Costa VM, King CE, Kalan L, Morar M, Sung WW, Schwarz C, et al. Antibiotic resistance is ancient.Nature. 2011;477:457–61. [DOI] [PubMed]
Andersson DI, Hughes D. Antibiotic resistance and its cost: is it possible to reverse resistance?Nat Rev Microbiol. 2010;8:260–71. [DOI] [PubMed]
Cassir N, Rolain JM, Brouqui P. A new strategy to fight antimicrobial resistance: the revival of old antibiotics.Front Microbiol. 2014;5:551. [DOI] [PubMed] [PMC]
Theuretzbacher U, Outterson K, Engel A, Karlén A. The global preclinical antibacterial pipeline.Nat Rev Microbiol. 2020;18:275–85. [DOI] [PubMed] [PMC]
Duval RE, Grare M, Demoré B. Fight against antimicrobial resistance: we always need new antibacterials but for right bacteria.Molecules. 2019;24:3152. [DOI] [PubMed] [PMC]
Santajit S, Indrawattana N. Mechanisms of antimicrobial resistance in ESKAPE pathogens.BioMed Res Int. 2016;2016:2475067. [DOI] [PubMed] [PMC]
Ma YX, Wang CY, Li YY, Li J, Wan QQ, Chen JH, et al. Considerations and caveats in combating ESKAPE pathogens against nosocomical infections.Adv Sci (Weinh). 2020;7:1901872.Erratum in: Adv Sci (Weinh). 2020;7:202000779. [DOI] [PubMed] [PMC]
Agarwal R, Bartsch SM, Kelly BJ, Prewitt M, Liu Y, Chen Y, et al. Newer glycopeptide antibiotics for treatment of complicated skin and soft tissue infections: systematic review, network meta-analysis and cost analysis.Clin Microbiol Infect. 2018;24:361–8. [DOI] [PubMed] [PMC]
Blaskovich MAT, Hansford KA, Butler MS, Jia Z, Mark AE, Cooper MA. Developments in glycopeptide antibiotics.ACS Infect Dis. 2018;4:715–35. [DOI] [PubMed] [PMC]
Bouza E, Muñoz P, Burillo A. The role of tedizolid in skin and soft tissue infections.Curr Opin Infect Dis. 2018;31:131–40. [DOI] [PubMed]
2021 Antibacterial agents in clinical and preclinical development: an overview and analysis [Internet].Geneva: World Health Organization; [cited 2023 Mar 16]. Available from: https://www.who.int/publications/i/item/9789240047655
Richter MF, Hergenrother PJ. The challenge of converting Gram-positive-only compounds into broad-spectrum antibiotics.Ann N Y Acad Sci. 2019;1435:18–38. [DOI] [PubMed] [PMC]
David MZ, Dryden M, Gottlieb T, Tattevin P, Gould IM. Recently approved antibacterials for methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive pathogens: the shock of the new.Int J Antimicrob Agents. 2017;50:303–7. [DOI] [PubMed]
Suleyman G, Alangaden G, Bardossy AC. The role of environmental contamination in the transmission of nosocomial pathogens and healthcare-associated infections.Curr Infect Dis Rep. 2018;20:12. [DOI] [PubMed]
Price MJ, Biava GC, Oser LB, Vogin EE, Steinfeld J, Ley LH. Bladder tumors in rats fed cyclohexylamine or high doses of a mixture of cyclamate and saccharin.Science. 1970;167:1131–2. [DOI] [PubMed]
Masui T, Mann MA, Borgeson DC, Garland ME, Okamura T, Fujii H, et al. Sequencing analysis of Ha-, Ki-, and N-ras genes in rat urinary bladder tumors induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and sodium saccharin.Terat Carcin Mutagen. 1993;13:225–33. [DOI] [PubMed]
Garland ME, Sakata T, Fisher MJ, Masui T, Cohen MS. Influences of diet and strain on the proliferative effect on the rat urinary bladder induced by sodium saccharin.Cancer Res. 1989;49:3789–94. [PubMed]
Groutas WC, Houser-Archield N, Chong LS, Venkataraman R, Epp JB, Huang H, et al. Efficient inhibition of human-leukocyte elastase and cathepsin-G by saccharin derivatives.J Med Chem. 1993;36:3178–81. [DOI] [PubMed]
Groutas WC, Chong LS, Venkataraman R, Kuang R, Epp JB, Houser-Archield N, et al. Amino acid-derivative phthalimide and saccharin derivatives as inhibitors of human leukocyte elastase, cathepsin G, and proteinase 3.Arch Biochem Biophys. 1996;332:335–40. [DOI] [PubMed]
Groutas WC, Epp JB, Venkataraman R, Kuang R, Truong TM, McClenahan JJ, et al. Design, synthesis, and in vitro inhibitory activity toward human leukocyte elastase, cathepsin G, and proteinase 3 of saccharin-derived sulfones and congeners.Bioorg Med Chem. 1996;4:1393–400. [DOI] [PubMed]
Elghamry I, Youssef MM, Al-Omair MA, Elsawy H. Synthesis, antimicrobial, DNA cleavage and antioxidant activities of tricyclic sultams derived from saccharin.Eur J Med Chem. 2017;139:107–13. [DOI] [PubMed]
Guenther U, Wrigge H, Theuerkauf N, Boettcher MF, Wensing G, Zinserling J, et al. Repinotan, a selective 5-HT1A-R-agonist, antagonizes morphine-induced ventilator depression in anesthetized rats.Anesth Analg. 2010;111:901–7. [DOI] [PubMed]
Malinka W, Ryng S, Sieklucka-Dziuba M, Rajtar G, Gownial A, Kleinrok Z. 2-Substituted-3-oxoisothiazolo[5,4-b]pyridines as potential central nervous system and antimycobacterial agents.Farmaco. 1998;53:504–12. [DOI] [PubMed]
Malinka W, Sieklucka-Dziuba M, Rajtar G, Gownial A, Kleinrok Z. Synthesis and preliminary screening of derivatives of 2-(4-arylpiperazine-1-ylalkyl)-3-oxoisothiazolo[5,4,b]pyridines as CNS and antimycobacterial agents.Pharmazie. 2000;55:416–25.
Csakai A, Smith C, Davis E, Martinko A, Coulp S, Yin H. Saccharin derivatives as inhibitors of interferon-mediated inflammation.J Med Chem. 2014;57:5348–55. [DOI] [PubMed] [PMC]
Singh H, Chawla AS, Kapoor VK, Paul D, Malhotra RK. 4 Medicinal chemistry of tetrazoles.Prog Med Chem. 1980;17:151–83. [DOI]
Noda K, Saad Y, Kinoshita A, Boyle TP, Graham RM, Husain A, et al. Tetrazole and carboxylate receptor antagonists bind to the same subsite by different mechanisms (*).J Biol Chem. 1995;270:2284–9. [DOI] [PubMed]
Mavromoustakos T, Kolocouris A, Zervou M, Roumelioti P, Matsoukas J, Weisemann R. An effort to understand the molecular basis of hypertension through the study of conformational analysis of Losartan and Sarmesin using a combination of nuclear magnetic resonance spectroscopy and theoretical calculations.J Med Chem. 1999;42:1714–22. [DOI] [PubMed]
Toney JH, Fitzgerald PMD, Grover-Sharma N, Olson SH, May WJ, Sundelof JG, et al. Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of Bacteroides fragilis metallo-β-lactamase.Chem Biol. 1998;5:185–96. [DOI] [PubMed]
Gao C, Chang L, Xu Z, Yan XF, Ding C, Zhao F, et al. Recent advances of tetrazole derivatives as potential anti-tubercular and anti-malarial agents.Eur J Med Chem. 2019;163:404–12. [DOI] [PubMed]
Hashimoto Y, Ohashi R, Kurosawa Y, Minami K, Kaji H, Hayashida K, et al. Pharmacologic profile of TA-606, a novel angiotensin II-receptor antagonist in the rat.J Cardiovasc Pharmacol. 1998;31:568–75. [DOI] [PubMed]
De Sarro A, Ammendola D, Zappala M, Grasso S, De Sarro GB. Relationship between structure and convulsant properties of some beta-lactam antibiotics following intracerebroventricular microinjection in rats.Antimicrob Agents Chemother. 1995;39:232–7. [DOI] [PubMed] [PMC]
Tamura Y, Watanabe F, Nakatani T, Yasui K, Fuji M, Komurasaki T, et al. Highly selective and orally active inhibitors of type IV collagenase (MMP-9 and MMP-2): N-sulfonylamino acid derivatives.J Med Chem. 1998;41:640–9. [DOI] [PubMed]
Abell AD, Foulds GJ. Synthesis of a cis-conformationally restricted peptide bond isostere and its application to the inhibition of the HIV-1 protease.J Chem Soc Perkin Trans 1. 1997:2475–82. [DOI]
Almajan GL, Barbuceanu SF, Bancescu G, Saramet I, Saramet G, Draghici C. Synthesis and antimicrobial evaluation of some fused heterocyclic [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives.Eur J Med Chem. 2010;45:6139–46. [DOI] [PubMed]
Noolvi MN, Patel HM, Singh N, Gadad AK, Cameotra SS, Badiger A. Synthesis and anticancer evaluation of novel 2-cyclopropylimidazo[2,1-b][1,3,4]-thiadiazole derivatives.Eur J Med Chem. 2011;46:4411–8. [DOI] [PubMed]
Liu XH, Shi YX, Ma Y, Zhang CY, Dong WL, Pan L, et al. Synthesis, antifungal activities and 3D-QSAR study of N-(5-substituted-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamides.Eur J Med Chem. 2009;44:2782–6. [DOI] [PubMed]
Hafez HN, Hegab MI, Ahmed-Farag IS, el-Gazzar ABA. A facile regioselective synthesis of novel spiro-thioxanthene and spiro-xanthene-9’,2-[1,3,4]thiadiazole derivatives as potential analgesic and anti-inflammatory agents.Bioorg Med Chem Lett. 2008;18:4538–43. [DOI] [PubMed]
Kolavi G, Hegde V, Khazi I, Gadad P. Synthesis and evaluation of antitubercular activity of imidazo[2,1-b][1,3,4]thiadiazole derivatives.Bioorg Med Chem. 2006;14:3069–80. [DOI] [PubMed]
Khan I, Ali S, Hameed S, Rama NH, Hussain MT, Wadood A, et al. Synthesis, antioxidant activities and urease inhibition of some new 1,2,4-triazole and 1,3,4-thiadiazole derivatives.Eur J Med Chem. 2010;45:5200–7. [DOI] [PubMed]
Jatav V, Mishra P, Kashaw S, Stables JP. CNS depressant and anticonvulsant activities of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones.Eur J Med Chem. 2008;43:1945–54. [DOI] [PubMed]
Clerici F, Pocar D, Guido M, Loche A, Perlini V, Brufani M. Synthesis of 2-amino-5-sulfanyl-1,3,4-thiadiazole derivatives and evaluation of their antidepressant and anxiolytic activity.J Med Chem. 2001;44:931–6. [DOI] [PubMed]
Hasui T, Matsunaga N, Ora T, Ohyabu N, Nishigaki N, Imura Y, et al. Identification of benzoxazin-3-one derivatives as novel, potent, and selective nonsteroidal mineralocorticoid receptor antagonists.J Med Chem. 2011;54:8616–31. [DOI] [PubMed]
Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, et al.; Wilderness Medical Society. Wilderness Medical Society Consensus Guidelines for the prevention and treatment of acute altitude illness.Wilderness Environ Med. 2010;21:146–55.Erratum in: Wilderness Environ Med. 2010;21:386. [DOI] [PubMed]
Wolf P. Acute drug administration in epilepsy: a review.CNS Neurosci Ther. 2011;17:442–8. [DOI] [PubMed] [PMC]
Kaur IP, Smitha R, Aggarwal D, Kapil M. Acetazolamide: future perspective in topical glaucoma therapeutics.Int J Pharm. 2002;248:1–14. [DOI] [PubMed]
Russell MB, Ducros A. Sporadic and familial hemiplegic migraine: pathophysiology mechanisms, clinical characteristics, diagnosis, and management.Lancet Neurol. 2011;10:457–70. [DOI] [PubMed]
Jalandhara NB, Patel A, Arora RR, Jalandhara P. Obstructive sleep apnea: a cardiopulmonary perspective and medical therapeutics.Am J Ther. 2009;16:257–63. [DOI] [PubMed]
Leal JF, Guerreiro B, Amado PSM, Fernandes AL, Barreira L, Paixão JA, et al. On the development of selective chelators for cadmium: synthesis, structure and chelating properties of 3-((5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)amino)benzo[d]isothiazole 1,1-dioxide, a novel thiadiazolyl saccharinate.Molecules. 2021;26:1501. [DOI] [PubMed] [PMC]
Rode HB, Sprang T, Besch A, Loose J, Otto HH. Pseudosaccharin amine derivatives: synthesis and elastase inhibitory activity.Pharmazie. 2005;60:723–31. [PubMed]
Weinstein MP, Lewis JS, Patel JB, Limbago B, Bobenchik AM, Mathers AJ, et al., editors. Performance standards for antimicrobial susceptibility testing. 29th ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2019.
Raimundo L, Paterna A, Calheiros J, Ribeiro J, Cardoso DSP, Piga I, et al. BBIT20 inhibits homologous DNA repair with disruption of the BRCA1–BARD1 interaction in breast and ovarian cancer.Br J Pharmacol. 2021;178:3627–47.Erratum in: Br J Pharmacol. 2022;179:1470–2. [DOI] [PubMed] [PMC]
Magalhães M, Farinha D, de Lima MCP, Faneca H. Increased gene delivery efficiency and specificity of a lipid-based nanosystem incorporating a glycolipid.Int J Nanomedicine. 2014;9:4979–89. [DOI] [PubMed] [PMC]
Ismael A, Henriques MSC, Marques C, Rodrigues M, Barreira L, Paixão JA, et al. Exploring saccharinate-tetrazoles as selective Cu(II) ligands: structure, magnetic properties and cytotoxicity of copper(II) complexes based on 5-(3-aminosaccharyl)-tetrazoles.RSC Adv. 2016;6:71628–37. [DOI]
Frija LMT, Alegria ECBA, Sutradhar M, Cristiano MLS, Ismael A, Kopylovich MN, et al. Copper(II) and cobalt(II) tetrazole-saccharinate complexes as effective catalysts for oxidation of secondary alcohols.J Mol Catal A Chem. 2016;425:283–90. [DOI]
Frija LMT, Fausto R, Loureiro RMS, Cristiano MLS. Synthesis and structure of novel benzisothiazole-tetrazolyl derivatives for potential application as nitrogen ligands.J Mol Catal A Chem. 2009;305:142–6. [DOI]
Ismael A, Paixão JA, Fausto R, Cristiano MLS. Molecular structure of nitrogen-linked methyltetrazole-saccharinates.J Mol Struct. 2012;1023:128–42. [DOI]
Cabral L, Brás E, Henriques M, Marques C, Frija LMT, Barreira L, et al. Synthesis, structure, and cytotoxicity of a new sulphanyl-bridged thiadiazolyl-saccharinate conjugate: the relevance of S…N interaction.Chemistry. 2018;24:3251–62. [DOI] [PubMed]
Frija LMT, Ntungwe E, Sitarek P, Andrade JM, Toma M, Śliwiński T, et al. In vitro assessment of antimicrobial, antioxidant, and cytotoxic properties of saccharin–tetrazolyl and –thiadiazolyl derivatives: the simple dependence of the pH value on antimicrobial activity.Pharmaceuticals (Basel). 2019;12:167. [DOI] [PubMed] [PMC]
Kamble DP, Shankarwar AG, Mane YD, Tigote RM, Sarnikar YP, Madje BR. Synthesis, characterization and antimicrobial evaluation of new 3- (alkyl/arylamino) benzo [d] isothiazole 1,1- derivatives.Orient J Chem. 2021;37:797–804. [DOI]
