References

1. Gaynes, R. The discovery of Penicillin—New insights after more than 75 years of clinical use. Emerg. Infect. Dis. 2017, 23, 849–853.
2. Horner, W.H. Streptomycin. In Biosynthesis; Springer: Berlin/Heidelberg, Germany, 1967; pp. 373–399.
3. Global Pharma News and Resources. Available online: (accessed on 8 September 2020).
4. Tacconelli, E.; Carrara, E.; Savoldi, A.; Harbarth, S.; Mendelson, M.; Monnet, D.L.; Pulcini, C.; Kahlmeter, G.; Kluytmans, J.; Carmeli, Y.; et al. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect. Dis. 2018, 18, 318–327.
5. Mulani, M.S.; Kamble, E.E.; Kumkar, S.N.; Tawre, M.S.; Pardesi, K.R. Emerging strategies to combat ESKAPE pathogens in the era of antimicrobial resistance: A review. Front. Microbiol. 2019, 10, 1–24.
6. Tanwar, J.; Das, S.; Fatima, Z.; Hameed, S. Multidrug resistance: An emerging crisis. Interdiscip. Perspect. Infect. Dis. 2014, 2014, 541340.
7. De Oliveira, D.M.P.; Forde, B.M.; Kidd, T.J.; Harris, P.N.; Schembri, M.A.; Beatson, S.A.; Paterson, D.L.; Walker, M.J. Antimicrobial resistance in ESKAPE pathogens. Clin. Microbiol. Rev. 2020, 33, e00181-19.
8. Rice, L.B. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: No ESKAPE. J. Infect. Dis. 2008, 197, 1079–1081.
9. World Health Organization. Available online: (accessed on 10 November 2020).
10. World Health Organization. Available online: (accessed on 16 November 2020).
11. Nikaido, H. Multidrug resistance in bacteria. Annu. Rev. Biochem. 2009, 78, 119–146.
12. Santajit, S.; Indrawattana, N. Mechanisms of antimicrobial resistance in ESKAPE pathogens. BioMed Res. Int. 2016, 2016, 475067.
13. Sharifi-Rad, J.; Salehi, B.; Stojanović-Radić, Z.Z.; Fokou, P.V.T.; Sharifi-Rad, M.; Mahady, G.B.; Sharifi-Rad, M.; Masjedi, M.-R.; Lawal, T.O.; Ayatollahi, S.A.; et al. Medicinal plants used in the treatment of tuberculosis-ethnobotanical and ethnopharmacological approaches. Biotechnol. Adv. 2020, 44, 107629.
14. Tiwari Pandey, A.; Pandey, I.; Hachenberger, Y.; Krause, B.C.; Haidar, R.; Laux, P.; Luch, A.; Singh, M.P.; Singh, A.V. Emerging paradigm against global antimicrobial resistance via bioprospecting of mushroom into novel nanotherapeutics development. Trends Food Sci. Technol. 2020, 106, 333–344.
15. Tiwari Pandey, A.; Pandey, I.; Zamboni, P.; Gemmati, D.; Kanase, A.; Singh, A.V.; Singh, M.P. Traditional herbal remedies with a multifunctional therapeutic approach as an implication in COVID-19 associated co-infections. Coatings 2020, 10, 761.
16. Ansari, M.H.D.; Lavhale, S.; Kalunke, R.M.; Srivastava, P.L.; Pandit, V.; Gade, S.; Yadav, S.; Laux, P.; Luch, A.; Gemmati, D.; et al. Recent advances in plant nanobionics and nanobiosensors for toxicology applications. Curr. Nanosci. 2020, 16, 27–41.
17. Singh, V.; Kumar, V.; Kashyap, S.; Singh, A.V.; Kishore, V.; Sitti, M.; Saxena, P.S.; Srivastava, A. Graphene oxide synergistically enhances antibiotic efficacy in vancomycin-resistant Staphylococcus aureus. ACS Appl. Bio Mater. 2019, 2, 1148–1157.
18. Kurban, S.; Deniz, N.G.; Sayil, C.; Ozyurek, M.; Guclu, K.; Stasevych, M.; Zvarych, V.; Komarovska-Porokhnyavet, O.; Novikov, V. Synthesis, antimicrobial properties, and inhibition of catalase activity of 1,4-naphtho-and benzoquinone derivatives containing N-, S-, O-substituted. Heteroat. Chem. 2019, 2019, 1658417.
19. Sánchez-Calvo, J.M.; Barbero, G.R.; Guerrero-Vásquez, G.; Durán, A.G.; Macías, M.; Rodríguez-Iglesias, M.A.; Molinillo, J.M.; Macías, F.A. Synthesis, antibacterial and antifungal activities of naphthoquinone derivatives: A structure–activity relationship study. Med. Chem. Res. 2016, 25, 1274–1285.
20. Mathiyazhagan, K.; Kumaran, A.; Arjun, P. Isolation of natural naphthoquinones from Juglans regia and in vitro antioxidant and cytotoxic studies of naphthoquinones and the synthetic naphthofuran derivatives. Russ. J. Bioorganic Chem. 2018, 44, 346–353.
21. Salas, C.O.; Faúndez, M.; Morello, A.; Diego Maya, J.A.; Tapia, R. Natural and synthetic naphthoquinones active against Trypanosoma Cruzi: An initial step towards new drugs for Chagas disease. Curr. Med. Chem. 2011, 18, 144–161.
22. Jentzsch, J.; Koko, W.S.; Al Nasr, I.S.; Khan, T.A.; Schobert, R.; Ersfeld, K.; Biersack, B. New antiparasitic bis-naphthoquinone derivatives. Chem. Biodivers. 2020, 17, e1900597.
23. Lall, N.; Weiganand, O.; Hussein, A.A.; Meyer, J.J.M. Antifungal activity of naphthoquinones and triterpenes isolated from the root bark of Euclea natalensis. South Afr. J. Bot. 2006, 72, 579–583.
24. Wellington, K.W.; Nyoka, N.B.; McGaw, L.J. Investigation of the antibacterial and antifungal activity of thiolated naphthoquinones. Drug Dev. Res. 2019, 80, 386–394.
25. Tandon, V.K.; Singh, R.V.; Yadav, D.B. Synthesis and evaluation of novel 1,4-naphthoquinone derivatives as antiviral, antifungal and anticancer agents. Bioorg. Med. Chem. Lett. 2004, 14, 2901–2904.
26. Schuck, D.C.; Ferreira, S.B.; Cruz, L.N.; Da Rocha, D.R.; Moraes, M.S.; Nakabashi, M.; Rosenthal, P.J.; Ferreira, V.F.; Garcia, C.R. Biological evaluation of hydroxynaphthoquinones as anti-malarials. Malar. J. 2013, 12, 1–6.
27. Klaus, V.; Hartmann, T.; Gambini, J.; Graf, P.; Stahl, W.; Hartwig, A.; Klotz, L.-O. 1,4-Naphthoquinones as inducers of oxidative damage and stress signaling in HaCaT human keratinocytes. Arch. Biochem. Biophys. 2010, 496, 93–100.
28. Liang, W.; Cai, A.; Chen, G.; Xi, H.; Wu, X.; Cui, J.; Zhang, K.; Zhao, X.; Yu, J.; Wei, B.; et al. Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species. Sci. Rep. 2016, 6, 38267.
29. Liu, C.; Shen, G.N.; Luo, Y.H.; Piao, X.J.; Jiang, X.Y.; Meng, L.Q.; Wang, Y.; Zhang, Y.; Wang, J.R.; Wang, H.; et al. Novel 1,4-naphthoquinone derivatives induce apoptosis via ROS-mediated P38/MAPK, Akt and STAT3 signaling in human hepatoma Hep3B cells. Int. J. Biochem. Cell Biol. 2018, 96, 9–19.
30. Lim, M.-Y.; Jeon, J.-H.; Jeong, E.-Y.; Lee, C.-H.; Lee, H.-S. Antimicrobial activity of 5-hydroxy-1,4-naphthoquinone isolated from Caesalpinia sappan toward intestinal bacteria. Food Chem. 2007, 100, 1254–1258.
31. Periasamy, H.; Iswarya, S.; Pavithra, N.; Senthilnathan, S.; Gnanamani, A. In vitro antibacterial activity of plumbagin isolated from Plumbago zeylanica L. against methicillin-resistant Staphylococcus aureus. Lett. Appl. Microbiol. 2019, 69, 41–49.
32. Patwardhan, R.B.; Shinde, P.S.; Chavan, K.R.; Devale, A. Reversal of plasmid encoded antibiotic resistance from nosocomial pathogens by using Plumbago auriculata root extracts. Int. J. Curr. Microbiol. Appl. Sci. 2015, 2, 187–198.
33. Kaewbumrung, S.; Panichayupakaranant, P. Antibacterial activity of plumbagin derivative-rich Plumbago indica root extracts and chemical stability. Nat. Prod. Res. 2014, 28, 835–837.
34. Patwardhan, R.B.; Dhakephalkar, P.K.; Chopade, B.A.; Dhavale, D.D.; Bhonde, R.R. Purification and characterization of an active principle, lawsone, responsible for the plasmid curing activity of Plumbago zeylanica root extracts. Front. Microbiol. 2018, 9, 2618.
35. Tekin, V.; Muftuler, F.Z.B.; Guldu, O.K.; Kilcar, A.Y.; Medine, E.I.; Yavuz, M.; Unak, P.; Timur, S. Biological affinity evaluation of Lawsonia inermis origin lawsone compound and its radioiodinated form via in vitro methods. J. Radioanal. Nucl. Chem. 2015, 303, 701–708.
36. Huang, X.Y.; Fu, H.L.; Tang, H.Q.; Yin, Z.Q.; Zhang, W.; Shu, G.; Yin, L.Z.; Zhao, L.; Yan, X.R.; Lin, J.C. Optimization extraction of shikonin using ultrasound-assisted response surface methodology and antibacterial studies. Evid. Based Complement Alternat. Med. 2020, 2020, 1–4.
37. Lee, Y.S.; Lee, D.Y.; Kim, Y.B.; Lee, S.W.; Cha, S.W.; Park, H.W.; Kim, G.S.; Kwon, D.Y.; Lee, M.H.; Han, S.H. The mechanism underlying the antibacterial activity of shikonin against methicillin-resistant Staphylococcus aureus. Evid. Based Complement Alternat. Med. 2015, 2015, 520578.
38. Zani, C.L.; De Oliveira, A.B.; De Oliviera, G.G. Furanonaphthoquinones from Tabebuia Ochracea. Phytochemistry 1991, 30, 2379–2381.
39. Souza, M.A.; Johann, S.; Lima, L.A.R.d.S.; Campos, F.F.; Mendes, I.C.; Beraldo, H.; Souza-Fagundes, E.M.d.; Cisalpino, P.S.; Rosa, C.A.; Alves, T.M.d.A.; et al. The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives. Mem. Inst. Oswaldo Cruz. 2013, 108, 342–351.
40. Widhalm, J.R.; Rhodes, D. Biosynthesis and molecular actions of specialized 1,4-naphthoquinone natural products produced by horticultural plants. Hortic. Res. 2016, 3, 1–17.
41. Zhou, D.-Y.; Zhu, B.-W.; Wang, X.-D.; Qin, L.; Li, D.-M.; Miao, L.; Murata, Y. Stability of polyhydroxylated 1,4-naphthoquinone pigment recovered from spines of sea urchin Strongylocentrotus nudus. Int. J. Food Sci. Technol. 2012, 47, 1479–1486.
42. Carriço, M.d.P.S.B.; do Carmo Cardoso, M.F.; Da Silva, F.D.C.; Ferreira, V.F.; Lima, E.S.; Souza, J.V.B. Antifungal activity of synthetic naphthoquinones against dermatophytes and opportunistic fungi: Preliminary mechanism-of-action tests. Ann. Clin. Microbiol. Antimicrob. 2014, 13, 26.
43. Adusei, E.; Adosraku, R.K.; Oppong-Kyekyeku, J.; Amengor, C.D.; Jibira, Y. Resistance modulation action, time-kill kinetics assay, and inhibition of biofilm formation effects of plumbagin from Plumbago zeylanica Linn. J. Trop. Med. 2019, 2019, 31.
44. Vukic, M.D.; Vukovic, N.L.; Djelic, G.T.; Popovic, S.L.; Zaric, M.M.; Baskic, D.D.; Krstic, G.B.; Tesevic, V.V.; Kacaniova, M.M. Antibacterial and cytotoxic activities of naphthoquinone pigments from Onosma visianii Clem. EXCLI J. 2017, 16, 73–88.
45. Petrosyan, M.; Shcherbakova, Y.; Sahakyan, N.; Vardanyan, Z.; Poladyan, A.; Popov, Y.; Trchounian, A. Alkanna orientalis (L.) Boiss. Plant isolated cultures and antimicrobial activity of their extracts: Phenomenon, dependence on different factors and effects on some membrane-associated properties of bacteria. Plant Cell Tissue Organ Cult. 2015, 122, 727–738.
46. Wang, J.; Cheng, Y.; Wu, R.; Jiang, D.; Bai, B.; Tan, D.; Yan, T.; Sun, X.; Zhang, Q.; Wu, Z. Antibacterial activity of juglone against Staphylococcus aureus: From apparent to proteomic. Int. J. Mol. Sci. 2016, 17, 965.
47. Padhye, S.; Dandawate, P.; Yusufi, M.; Ahmad, A.; Sarkar, F.H. Perspectives on medicinal properties of plumbagin and its analogs. Med. Res. Rev. 2012, 32, 1131–1158.
48. Al-Mussawi, A.A. Isolation and identification of shikonin from Arnebia Decumbens L. and its antibacterial activity. Res. J. Appl. Sci. 2010, 6, 1452–1456.
49. Andújar, I.; Ríos, J.L.; Giner, R.M.; Recio, M.C. Pharmacological properties of shikonin-a review of literature since 2002. Planta Med. 2013, 79, 1685–1697.
50. Aljanaby, A.J. Antibacterial Activity of an aqueous extracts of Alkanna tinctoria roots against drug resistant aerobic pathogenic bacteria isolated from patients with burns infections. Russ. Open Med. J. 2018, 7, e0104.
51. De Almeida, E.R. Preclinical and clinical studies of lapachol and beta-lapachone. Open Nat. Prod. J. 2009, 2, 42–47.
52. Balachandran, C.; Al-Dhabi, N.A.; Duraipandiyan, V.; Ignacimuthu, S. Bluemomycin, a new naphthoquinone derivative from Streptomyces sp. with antimicrobial and cytotoxic properties. Biotechnol. Lett. 2021, 43, 1–4.
53. Ravichandiran, P.; Sheet, S.; Premnath, D.; Kim, A.R.; Yoo, D.J. 1,4-Naphthoquinone analogues: Potent antibacterial agents and mode of action evaluation. Molecules 2019, 24, 1437.
54. Tandon, V.K.; Yadav, D.B.; Singh, R.V.; Chaturvedi, A.K.; Shukla, P.K. Synthesis and biological evaluation of novel (L)-α-amino acid methyl ester, heteroalkyl, and aryl substituted 1,4-naphthoquinone derivatives as antifungal and antibacterial agents. Bioorg. Med. Chem. Lett. 2005, 15, 5324–5328.
55. Sarkar, A.; Ghosh, S.; Shaw, R.; Patra, M.M.; Calcuttawala, F.; Mukherjee, N.; Gupta, S.K.D. Mycobacterium tuberculosis thymidylate synthase (ThyX) is a target for plumbagin, a natural product with antimycobacterial activity. PLoS ONE 2020, 15, e0228657.
56. Meah, M.S.; Lertcanawanichakul, M.; Pedpradab, P.; Lin, W.; Zhu, K.; Li, G.; Panichayupakaranant, P. Synergistic effect on anti-methicillin-resistant Staphylococcus aureus among combinations of α-mangostin-rich extract, lawsone methyl ether and ampicillin. Lett. Appl. Microbiol. 2020, 71, 510–519.
57. Song, R.; Yu, B.; Friedrich, D.; Li, J.; Shen, H.; Krautscheid, H.; Huang, S.D.; Kim, M.-H. Naphthoquinone-derivative as a synthetic compound to overcome the antibiotic resistance of methicillin-resistant S. aureus. Commun. Biol. 2020, 3, 1–11.
58. Linzner, N.; Fritsch, V.N.; Busche, T.; Tung, Q.N.; Loi, V.V.; Bernhardt, J.; Kalinowski, J.; Antelmann, H. The plant-derived naphthoquinone lapachol causes an oxidative stress response in Staphylococcus aureus. Free Radic. Biol. Med. 2020, 158, 126–136.
59. Figueredo, F.G.; Ramos, I.T.L.; Paz, J.A.; Silva, T.M.S.; Camara, C.A.; Oliveira-Tintino, C.D.d.M.; Relison Tintino, S.; de Farias, P.A.M.; Coutinho, H.D.M.; Fonteles, M.M.d.F. In silico evaluation of the antibacterial and modulatory activity of lapachol and nor-lapachol derivates. Microb. Pathog. 2020, 144, 104181.
60. Choudhari, D.; Salunke-Gawali, S.; Chakravarty, D.; Shaikh, S.R.; Lande, D.N.; Gejji, S.P.; Rao, P.K.; Satpute, S.; Puranik, V.G.; Gonnade, R. Synthesis and biological activity of imidazole based 1,4-naphthoquinones. New J. Chem. 2020, 44, 6889–6901.
61. Choudhari, D.; Chakravarty, D.; Lande, D.N.; Parveen, S.; Gejji, S.P.; Kodam, K.M.; Salunke-Gawali, S. Crystal structures and biological activity of homologated (N)-n-alkylammonium salts of 2-bromo-3-oxido-1,4-naphthoquinone. Struct. Chem. 2019, 30, 2257–2270.
62. Andrade, J.C.; Morais Braga, M.F.B.; Guedes, G.M.M.; Tintino, S.R.; Freitas, M.A.; Quintans, L.J.; Menezes, I.R.A.; Coutinho, H.D.M. Menadione (vitamin K) enhances the antibiotic activity of drugs by cell membrane permeabilization mechanism. Saudi J. Biol. Sci. 2017, 24, 59–64.
63. Moreira, C.S.; Silva, A.; Novais, J.S.; Sá Figueiredo, A.M.; Ferreira, V.F.; da Rocha, D.R.; Castro, H.C. Searching for a potential antibacterial lead structure against bacterial biofilms among new naphthoquinone compounds. J. Appl. Microbiol. 2017, 122, 651–662.
64. Janeczko, M.; Demchuk, O.M.; Strzelecka, D.; Kubiński, K.; Masłyk, M. New family of antimicrobial agents derived from 1,4-naphthoquinone. Eur. J. Med. Chem. 2016, 124, 1019–1025.
65. Qiu, H.Y.; Wang, P.F.; Wang, Z.Z.; Luo, Y.L.; Hu, D.Q.; Qi, J.L.; Lu, G.H.; Pang, Y.J.; Yang, R.W.; Zhu, H.L.; et al. Shikonin derivatives as inhibitors of tyrosyl-TRNA synthetase: Design, synthesis and biological evaluation. RSC Adv. 2016, 6, 83003–83010.
66. Zmantar, T.; Miladi, H.; Kouidhi, B.; Chaabouni, Y.; Slama, R.B.; Bakhrouf, A.; Mahdouani, K.; Chaieb, K. Use of juglone as antibacterial and potential efflux pump inhibitors in Staphylococcus aureus isolated from the oral cavity. Microb. Pathog. 2016, 101, 44–49.
67. Ravichandiran, P.; Premnath, D.; Vasanthkumar, S. Synthesis, molecular docking and antibacterial evaluation of 2-(4-(4-aminophenylsulfonyl) phenylamino)-3-(thiophen-2-ylthio) naphthalene-1,4-dione derivatives. Front. Chem. Sci. Eng. 2015, 9, 46–56.
68. Sreelatha, T.; Kandhasamy, S.; Dinesh, R.; Shruthy, S.; Shweta, S.; Mukesh, D.; Karunagaran, D.; Balaji, R.; Mathivanan, N.; Perumal, P.T. Synthesis and sar study of novel anticancer and antimicrobial naphthoquinone amide derivatives. Bioorg. Med. Chem. Lett. 2014, 24, 3647–3651.
69. Schlievert, P.M.; Merriman, J.A.; Salgado-Pabón, W.; Mueller, E.A.; Spaulding, A.R.; Vu, B.G.; Chuang-Smith, O.N.; Kohler, P.L.; Kirby, J.R. Menaquinone analogs inhibit growth of bacterial pathogens. Antimicrob. Agents Chemother. 2013, 57, 5432–5437.
70. Rahmoun, N.M.; Boucherit-Otmani, Z.; Boucherit, K.; Benabdallah, M.; Villemin, D.; Choukchou-Braham, N. Antibacterial and antifungal activity of lawsone and novel naphthoquinone derivatives. Med. Mal. Infect. 2012, 42, 270–275.
71. Mathew, R.; Kruthiventi, A.K.; Prasad, J.V.; Kumar, S.P.; Srinu, G.; Chatterji, D. Inhibition of mycobacterial growth by plumbagin derivatives. Chem. Biol. Drug Des. 2010, 76, 34–42.
72. Tandon, V.K.; Maurya, H.K.; Mishra, N.N.; Shukla, P.K. Design, synthesis and biological evaluation of novel nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents. Eur. J. Med. Chem. 2009, 44, 3130–3137.
73. Medina, L.F.C.; Hertz, P.F.; Stefani, V.; Henriques, J.A.P.; Zanotto-Filho, A.; Brandelli, A. Aminonaphthoquinone induces oxidative stress in Staphylococcus aureus. Biochem. Cell Biol. 2006, 84, 720–727.
74. Yap, J.K.Y.; Tan, S.Y.Y.; Tang, S.Q.; Thien, V.K.; Chan, E.W.L. Synergistic antibacterial activity between 1,4-naphthoquinone and β-lactam antibiotics against methicillin-resistant Staphylococcus aureus. Microb. Drug Resist. 2021, 27, 234–240.