Structural Modifications for Biological Activity Enhancements in Thiosemicarbazone Scaffolds and Their Metal Complexes

Abstract

The molecular weight of a typical small molecule drug is usually less than 500 Da. Small molecules can influence the function of different proteins by interacting with their targets and forming complexes. Thiosemicarbazones (TSCs) are biologically important Schiff base ligands. Due to their considerable biological importance, they have been explored for an extended period. TSC complexes exhibit structural diversity, varied bonding patterns, and hold promise for their biological importance, as well as ion-sensing properties. This review explores the medicinal applications of TSC complexes and the effect of different factors like molecular weight, structural alterations, presence of benzene ring and electron-donating and -withdrawing groups in the TSC moiety. Molecules in compliance with Lipinski’s rule have enhanced activity. Complexes with low molecular weight also possessed better absorption, distribution, metabolism, and excretion (ADME) characteristics, and good to moderate bioactivity scores. Mixed-ligand complexes have also been discussed, showing that synergetic effect may enhance the overall stability of the complex. Small molecules can be utilized as medicinal agents and as chemical probes for the exploration of new drug targets and through structural biology crucial interactions between the molecules and drug targets can be comprehended, thereby propelling target-based drug discovery.

1 Introduction: Small Therapeutic Molecules

2 TSCs as Potent Schiff Bases

2.1 Biological Activity of TSCs and Their Complexes

2.1.1 Anticancer Properties

2.1.2 Antibacterial Activity

2.1.3 Antiviral Activity

2.1.4 Antimalarial Activity

2.1.5 Antifungal Activity

3 Biological Activity: Factors of Consideration

3.1 Molecular Weight

3.2 Structural Alterations

3.3 Presence of Aromatic Rings and Electron-Donating or -Withdrawing Groups

4 Mixing and Permutations of Ligands

5 Mechanistic Insights

6 Activity of Hybrid TSCs

7 Future Prospects

7.1 Structure-Activity Relation (SAR) Studies

7.2 Donor Atoms and Chelation

7.3 Metal Ion Coordination

7.4 Factors Affecting Biological Activity

7.5 Pharmacokinetic Profiling

8 Conclusion

Key words

human health - medicine - Schiff bases - thiosemicarbazones - Lipinski’s rule

Publication History

Received: 10 April 2025

Accepted after revision: 04 July 2025

Accepted Manuscript online:
04 July 2025

Article published online:
05 August 2025

• References

• 1 Stockwell BR. Nature 2004; 432: 846
• 2 Hoelder S, Clarke PA, Workman P. Mol. Oncol. 2012; 6: 155
• 3 Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Adv. Drug Delivery Rev. 1997; 23: 3
• 4 Daniels DL, Riching KM, Urh M. Drug Discovery Today: Technol. 2019; 31: 61
• 5 Scott DE, Bayly AR, Abell C, Skidmore J. Nat. Rev. Drug Discovery 2016; 15: 533
• 6 Wagner BK, Schreiber SL. Cell Chem. Biol. 2016; 23: 3
• 7 Wagner BK. Expert Opin. Drug Discovery 2016; 11: 121
• 8 Johannessen CM, Clemons PA, Wagner BK. Trends Genet. 2015; 31: 16
• 9 Jang BS. Toxicol. Res. 2013; 29: 1
• 10 Ashburn TT, Thor KB. Nat. Rev. Drug Discovery 2004; 3: 673
• 11 Brown DG, Boström J. J. Med. Chem. 2018; 61: 9442
• 12 Lombardino JG, Lowe JA. Nat. Rev. Drug Discovery 2004; 3: 853
• 13 Stocks M. The Small Molecule Drug Discovery Process – from Target Selection to Candidate Selection. In Introduction to Biological and Small Molecule Drug Research and Development: Theory and Case Studies. Ganellin CR, Jefferis R, Roberts SM. Academic Press/Elsevier; Oxford, UK: 2013: 81-126
• 14 Mohs RC, Greig NH. Alzheimer’s & Dementia: Translational Research & Clinical Interventions 2017; 3: 651
• 15 Carnero A. Clin. Transl. Oncol. 2006; 8: 482
• 16 Moitessier N, Pottel J, Therrien E, Englebienne P, Liu Z, Tomberg A, Corbeil CR. Acc. Chem. Res. 2016; 49: 1646
• 17 Anderson AC. Chem. Biol. 2003; 10: 787
• 18 Ou-Yang SS, Lu JY, Kong XQ, Liang ZJ, Luo C, Jiang H. Acta Pharmacol. Sin. 2012; 33: 1131
• 19 Singh M, Tam B, Akabayov B. Molecules 2018; 23: 233
• 20 Erlanson DA, Fesik SW, Hubbard RE, Jahnke W, Jhoti H. Nat. Rev. Drug Discovery 2016; 15: 605
• 21 Goodnow RA, Dumelin CE, Keefe AD. Nat. Rev. Drug Discovery 2017; 16: 131
• 22 Chan AI, McGregor LM, Liu DR. Curr. Opin. Chem. Biol. 2015; 26: 55
• 23 Gerry CJ, Wawer MJ, Clemons PA, Schreiber SL. J. Am. Chem. Soc. 2019; 141: 10225
• 24 Corsello SM, Bittker JA, Liu Z, Gould J, McCarren P, Hirschman JE, Johnston SE, Vrcic A, Wong B, Khan M, Asiedu J. Nat. Med. 2017; 23: 405
• 25 Mullard A. Nat. Rev. Drug Discovery 2018; 17: 534
• 26 Schneider P, Walters WP, Plowright AT, Sieroka N, Listgarten J, Goodnow RA. Jr, Fisher J, Jansen JM, Duca JS, Rush TS, Zentgraf M. Nat. Rev. Drug Discovery 2020; 19: 353
• 27 Dahlin JL, Nissink JW. M, Strasser JM, Francis S, Higgins L, Zhou H, Zhang Z, Walters MA. J. Med. Chem. 2015; 58: 2091
• 28 Baell J, Walters MA. Nature 2014; 513: 481
• 29 Hughes J, Rees S, Kalindjian S, Philpott K. Br. J. Pharmacol. 2011; 162: 1239
• 30 An WF, Tolliday N. Mol. Biotechnol. 2010; 45: 180
• 31 Duggirala NK, Perry ML, Almarsson Ö, Zaworotko MJ. Chem. Commun. 2016; 52: 640
• 32 Congreve M, Murray CW, Blundell TL. Drug Discovery Today 2005; 10: 895
• 33 Ito T, Tori M, Hashigaki S, Kimura N, Sato K, Ohki E, Sawaki A, Okusaka T. Jpn. J. Clin. Oncol. 2019; 49: 354
• 34 Procopio G, Apollonio G, Cognetti F, Miceli R, Milella M, Mosca A, Chiuri VE, Bearz A, Morelli F, Ortega C, Atzori F. Eur. Urol. Oncol. 2019; 2: 699
• 35 Verschuur AC, Bajèiová V, Mascarenhas L, Khosravan R, Lin X, Ingrosso A, Janeway KA. Cancer Chemother. Pharmacol. 2019; 84: 41
• 36 Zahoor H, Mir MC, Barata PC, Stephenson AJ, Campbell SC, Fergany A, Dreicer R, Garcia JA. Invest. New Drugs 2019; 37: 1231
• 37 Mammatas LH, Zandvliet AS, Rovithi M, Honeywell RJ, Swart EL, Peters GJ, Menke-van der Houven van Oordt CW, Verheul HM. W. Cancer Chemother. Pharmacol. 2020; 85: 931
• 38 Ruanglertboon W, Sorich MJ, Rowland A, Hopkins AM. Int. J. Clin. Oncol. 2020; 25: 1672
• 39 Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ. Clin. Cancer Res. 2003; 9: 327
• 40 Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS. N. Engl. J. Med. 2011; 364: 501
• 41 Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y. Cancer Res. 2004; 64: 7099
• 42 Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D, Wilhelm S, Lynch M, Carter C. Cancer Res. 2006; 66: 11851
• 43 Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J. Lancet Oncol. 2009; 10: 25
• 44 Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M. N. Engl. J. Med. 2005; 353: 123
• 45 Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y. Lancet 2008; 372: 1809
• 46 Vigato PA, Tamburini S. Coord. Chem. Rev. 2004; 248: 1717
• 47 Salvat A, Antonnacci L, Fortunato RH, Suarez EY, Godoy HM. Lett. Appl. Microbiol. 2001; 32: 293
• 48 Al-Kahraman YM, Madkour HM, Ali D, Yasinzai M. Molecules 2010; 15: 660
• 49 Dhar DN, Taploo CL. J. Sci. Ind. Res. 1982; 41: 501
• 50 Abd-Elzaher MM, Labib AA, Mousa HA, Moustafa SA, Ali MM, El-Rashedy AA. Beni-Suef Univ. J. Basic Appl. Sci. 2016; 5: 85
• 51 Hashmi K, Satya, Gupta S, Siddique A, Khan T, Joshi S. J. Trace Elem. Med. Biol. 2023; 79: 127245
• 52 Ghanghas P, Choudhary A, Kumar D, Poonia K. Inorg. Chem. Commun. 2021; 130: 108710
• 53 Pervaiz M, Sadiq S, Sadiq A, Younas U, Ashraf A, Saeed Z, Zuber M, Adnan A. Coord. Chem. Rev. 2021; 447: 214128
• 54 Ali A, Pervaiz M, Saeed Z, Younas U, Bashir R, Ullah S, Bukhari SM, Ali F, Jelani S, Rashid A, Adnan A. Inorg. Chem. Commun. 2022; 145: 109903
• 55 Liao Y, Yao Y, Yu Y, Zeng Y. Colloids Interface Sci. Commun. 2018; 25: 1
• 56 Theuretzbacher U, Bush K, Harbarth S, Paul M, Rex JH, Tacconelli E, Thwaites GE. Nat. Rev. Microbiol. 2020; 18: 286
• 57 Manikandan S, Thirunarayanan G. Int. J. Appl. Eng. Res. 2018; 13: 11077
• 58 Chemchem M, Menacer R, Merabet N, Bouridane H, Yahiaoui S, Moussaoui S, Belkhiri L. J. Mol. Struct. 2020; 1208: 127853
• 59 Damit NS, Hamid MH, Rahman NS, Ilias SN, Keasberry NA. Inorg. Chim. Acta 2021; 527: 120557
• 60 Wei L, Tan W, Zhang J, Mi Y, Dong F, Li Q, Guo Z. Polymers 2019; 11: 371
• 61 Elangovan N, Gangadharappa B, Thomas R, Irfan A. J. Mol. Struct. 2022; 1250: 131700
• 62 Pervaiz M, Ahmad I, Yousaf M, Kirn S, Munawar A, Saeed Z, Adnan A, Gulzar T, Kamal T, Ahmad A, Rashid A. Spectrochim. Acta, Part A 2019; 206: 642
• 63 Sinha A, Chaudhary R, Reddy DS, Kongot M, Kurjogi MM, Kumar A. Heliyon 2022; 8: e10125
• 64 Xia Y, Liu X, Zhang L, Zhang J, Li C, Zhang N, Xu H, Li Y. Cancer Cell Int. 2019; 19: 81
• 65 Beč A, Cindrić M, Persoons L, Banjanac M, Radovanović V, Daelemans D, Hranjec M. Molecules 2023; 28: 3720
• 66 Al Zoubi W, Al-Hamdani AA, Kaseem M. Appl. Organomet. Chem. 2016; 30: 810
• 67 Mahapatra DK, Dadure KM, Shivhare RS. MOJ Bioorg. Org. Chem. 2018; 2: 171
• 68 Vinusha HM, Kollur SP, Revanasiddappa HD, Ramu R, Shirahatti PS, Prasad MN, Chandrashekar S, Begum M. Results Chem. 2019; 1: 100012
• 69 Gupta S, Singh N, Khan T, Joshi S. Results Chem. 2022; 4: 100459
• 70 Kola I, Landis J. Nat. Rev. Drug Discovery 2004; 3: 711
• 71 Pelosi G. Open Crystallogr. J. 2010; 3: 16
• 72 Sartorelli AC, Booth BA. Cancer Res. 1967; 27: 1614
• 73 Nutting CM, Van Herpen CM. L, Miah AB, Bhide SA, Machiels JP, Buter J, Kelly C, De Raucourt D, Harrington KJ. Ann. Oncol. 2009; 20: 1275
• 74 Jamal SE, Iqbal A, Rahman AR, Khan T. J. Drug Delivery Ther. 2019; 9: 3
• 75 Kasuga NC, Sekino K, Ishikawa M, Honda A, Yokoyama M, Nakano S, Shimada N, Koumo C, Nomiya K. J. Inorg. Biochem. 2003; 96: 298
• 76 Brockman RW, Thomson JR, Bell MJ, Skipper HE. Cancer Res. 1956; 16: 167
• 77 French FA, Blanz EJ. Jr. Cancer Res. 1965; 25: 1454
• 78 Ferrari MB, Bisceglie F, Pelosi G, Tarasconi P, Albertini R, Dall’Aglio PP, Pinelli S, Bergamo A, Sava G. J. Inorg. Biochem. 2004; 98: 301
• 79 Quiroga AG, Ranninger CN. Coord. Chem. Rev. 2004; 248: 119
• 80 Çakmakçı ES, Subaşı E, Öztürk EJ, Şahiner A, Yüksel B. Ş. Inorg. Chim. Acta 2023; 551: 121462
• 81 Sharma N, Dhingra N, Singh HL. J. Mol. Struct. 2024; 1307: 138000
• 82 Diksha MK, Megha R, Kaur H, Yempally V. J. Mol. Struct. 2024; 1301: 137319
• 83 Halder S, Paul P, Peng SM, Lee GH, Mukherjee A, Dutta S, Sanyal U, Bhattacharya S. Polyhedron 2012; 45: 177
• 84 Sampath N, Mathews R, Ponnuswamy MN, Kang LW. Mol. Cryst. Liq. Cryst. 2010; 518: 151
• 85 Devi J, Yadav M, Jindal DK, Kumar D, Poornachandra Y. Appl. Organomet. Chem. 2019; 33: e5154
• 86 Ma ZY, Shao J, Bao WG, Qiang ZY, Xu JY. J. Coord. Chem. 2015; 68: 277
• 87 Zeglis BM, Divilov V, Lewis JS. J. Med. Chem. 2011; 54: 2391
• 88 Subasi E, Atalay EB, Erdogan D, Sen B, Pakyapan B, Kayali HA. Mater. Sci. Eng., C 2020; 106: 110152
• 89 Abdul Halim SN 'Ain, Nordin FJ, Mohd Abd Razak MR, Mohd Sofyan NR. F, Abdul Halim SN, Rajab NF, Sarip R. J. Coord. Chem. 2019; 72: 879
• 90 Bisceglie F, Pinelli S, Alinovi R, Goldoni M, Mutti A, Camerini A, Piola L, Tarasconi P, Pelosi G. J. Inorg. Biochem. 2014; 140: 111
• 91 Richter R, Beyer L. Bioinorg. Chem. Appl. 2008; 2008: 9
• 92 Saha DK, Padhye S, Sinn E, Newton C. Indian J. Chem., Sect. A 2002; 41: 279
• 93 Das M, Mukherjee A, Saha A, Bhattacharya S. J. of Organomet. Chem. 2025; 1030: 123567
• 94 Mann N, Oyeyemi I, Alajroush DR, Tonsel-White EA, Beebe SJ, Holder A. Undergrad. Res. Symp. 2023; 16 . https://digitalcommons.odu.edu/undergradsymposium/2023/posters/16?utm_source=digitalcommons.odu.edu%2Fundergradsymposium%2F2023%2Fposters%2F16&utm_medium=PDF&utm_campaign=PDFCoverPages
• 95 Lavanya M, Haribabu J, Ramaiah K, Yadav CS, Chitumalla RK, Jang J, Karvembu R, Reddy AV, Jagadeesh M. Inorg. Chim. Acta 2021; 524: 120440
• 96 Zheng XJ, Bell NL, Stevens CJ, Zhong YX, Schreckenbach G, Arnold PL, Love JB, Pan QJ. Dalton Trans. 2016; 45: 15910
• 97 Saha NC, Pradhan R, Das M, Khatun N, Mitra D, Samanta A, Slawin AM, Jana AD, Klanke J, Rentschler E. J. Coord. Chem. 2014; 67: 286
• 98 Zakir HM, Jesmin M, Ali SM. M. Asian J. Med. Pharm. Res. 2016; 6: 32
• 99 Agarwal RK, Prasad S. Bioinorg. Chem. Appl. 2005; 3: 271
• 100 El-Sawaf AK, El-Essawy F, Nassar AA, El-Samanody ES. A. J. Mol. Struct. 2018; 1157: 381
• 101 Jaafar A, Fix-Tailler A, Mansour N, Allain M, Shebaby WN, Faour WH, Tokajian S, El-Ghayoury A, Naoufal D, Bouchara JP, Larcher G. Appl. Organomet. Chem. 2020; 34: e5988
• 102 Khan T, Raza S, Lawrence A. Russ. J. Coord. Chem. 2022; 48: 877
• 103 Ali MA, Mirza AH, Monsur A, Hossain S, Nazimuddin M. Polyhedron 2001; 20: 1045
• 104 Belicchi-Ferrai M, Biscegli F, Pelosi G, Pinelli S, Tarascani P. Polyhedron 2007; 26: 5150
• 105 Hoggarth E, Martin AR, Storey NE, Young EH. P. Br. J. Pharmacol. Chemother. 1949; 4: 248
• 106 Bauer DJ. Ann. N. Y. Acad. Sci. 1965; 130: 110
• 107 Booth BA, Sartorelli AC. Mol. Pharmacol. 1967; 3: 290
• 108 Ma B, Goh BC, Tan EH, Lam KC, Soo R, Leong SS, Wang LZ, Mo F, Chan AT, Zee B, Mok T. Invest. New Drugs 2008; 26: 169
• 109 Akbari A, Ghateazadeh H, Takjoo R, Sadeghi-Nejad B, Mehrvar M, Mague JT. J. Mol. Struct. 2019; 1181: 287
• 110 Souza RA. C, Cunha VL, de Souza JH, Martins CH. G, Franca EF, Pivatto M, Ellena JA, Faustino LA, Patrocinio AO. T, Deflon VM, Maia PI. S, Oliveira CG. J. Inorg. Biochem. 2022; 237: 111995
• 111 Jan F, Idris S, Waheed M, Alam A, AlAsmari AF, Alasmari F, Khan M. J. Mol. Struct. 2024; 1311: 138459
• 112 Gan C, Cui J, Su S, Lin Q, Jia L, Fan L, Huang Y. Steroids 2014; 87: 99
• 113 Carcelli M, Montalbano S, Rogolino D, Gandin V, Miglioli F, Pelosi G, Buschini A. Inorg. Chim. Acta 2022; 533: 120779
• 114 Li BS. P, Zheng LM, King I, Doyle T, Chen SH. Curr. Med. Chem. 2012; 8: 121
• 115 Devi J, Kumar B, Taxak B. Inorg. Chem. Commun. 2022; 139: 109208
• 116 Xi R, Pun IH. Y, Menezes SV, Fouani L, Kalinowski DS, Huang ML, Zhang X, Richardson DR, Kovacevic Z. Mol. Pharmacol. 2017; 91: 499
• 117 Kanso F, Khalil A, Noureddine H, El-Makhour Y. Int. Immunopharmacol. 2021; 96: 107778
• 118 Oliveira CG, Maia PI. S, Souza PC, Pavan FR, Leite CQ, Viana RB, Batista AA, Nascimento OR, Deflon VM. J. Inorg. Biochem. 2014; 132: 21
• 119 Arancibia R, Quintana C, Biot C, Medina ME, Carrere-Kremer S, Kremer L, Klahn AH. Inorg. Chem. Commun. 2015; 55: 139
• 120 Volynets GP, Tukalo MA, Bdzhola VG, Derkach NM, Gumeniuk MI, Tarnavskiy SS, Starosyla SA, Yarmoluk SM. J. Antibiot. 2019; 72: 218
• 121 Khan A, Paul K, Singh I, Jasinski JP, Smolenski VA, Hotchkiss EP, Kelley PT, Shalit ZA, Kaur M, Banerjee S, Roy P. Dalton Trans. 2020; 49: 17350
• 122 Klayman DL, Bartosevich JF, Griffin TS, Mason CJ, Scovill JP. J. Med. Chem. 1979; 22: 855
• 123 Savir S, Liew JW. K, Vythilingam I, Lim YA. L, Tan CH, Sim KS, Lee VS, Maah MJ, Tan KW. J. Mol. Struct. 2021; 1242: 130815
• 124 Kumar B, Devi J, Dubey A, Tufail A, Sharma S. Inorg. Chem. Commun. 2024; 159: 111674
• 125 Lobana TS, Sharma R, Bawa G, Khanna S. Coord. Chem. Rev. 2009; 253: 977
• 126 Kowol CR, Trondl R, Heffeter P, Arion VB, Jakupec MA, Roller A, Galanski MS, Berger W, Keppler BK. J. Med. Chem. 2009; 52: 5032
• 127 Finch RA, Liu MC, Grill SP, Rose WC, Loomis R, Vasquez KM, Cheng YC. Sartorelli A. C. Biochem. Pharmacol. 2000; 59: 983
• 128 Kowol CR, Berger R, Eichinger R, Roller A, Jakupec MA, Schmidt PP, Arion VB, Keppler BK. J. Med. Chem. 2007; 50: 1254
• 129 Alam MS, Liu L, Lee DU. Chem. Pharm. Bull. 2011; 59: 1413
• 130 de Oliveira JF, Lima TS, Vendramini-Costa DB, de Lacerda Pedrosa SC. B, Lafayette EA, da Silva RM. F, de Almeida SM. V, de Moura RO, Ruiz AL. T. G, de Carvalho JE, de Lima MD. C. A. Eur. J. Med. Chem. 2017; 136: 305
• 131 Yee EM, Brandl MB, Black DS, Vittorio O, Kumar N. Bioorg. Med. Chem. Lett. 2017; 27: 2454
• 132 Chen J, Huang YW, Liu G, Afrasiabi Z, Sinn E, Padhye S, Ma Y. Toxicol. Appl. Pharmacol. 2004; 197: 40
• 133 Khan T, Ahmad R, Azad I, Raza S, Joshi S, Khan AR. Comput. Biol. Chem. 2018; 75: 178
• 134 Conner JD, Medawala W, Stephens MT, Morris WH, Deweese JE, Kent PL, Rice JJ, Jiang X, Lisic EC. Open J. Inorg. Chem. 2016; 6: 146
• 135 Lisic EC, Rand GV, Ngo L, Kent P, Rice J, Gerlach D, Papish ET, Jiang X. Open J. Med. Chem. 2018; 8: 30
• 136 Kovala-Demertzi D, Demertzis MA, Miller JR, Papadopoulou C, Dodorou C, Filousis G. J. Inorg. Biochem. 2001; 86: 555
• 137 Venkatesh K, Rayam P, Sekhar KC, Mukkanti K. Int. J. Appl. Biol. Pharm. 2016; 7: 258
• 138 Polo-Cerón D. Bioinorg. Chem. Appl. 2019; 2019: 3520837
• 139 Khan T, Zehra S, Alvi A, Mishra N, Lawrence R, Joshi S, Khan A. ChemistrySelect 2024; 9: e202400202
• 140 Khan SA, Asiri AM, Al-Amry K, Malik MA. Sci. World J. 2014; 2014: 592375
• 141 Kovala-Demertzi D, Varadinova T, Genova P, Souza P, Demertzis MA. Bioinorg. Chem. Appl. 2007; 2007: 56165
• 142 Padmanabhan P, Khaleefathullah S, Kaveri K, Palani G, Ramanathan G, Thennarasu S, Sivagnanam UT. J. Med. Virol. 2016; 89: 546
• 143 Bal TR, Anand B, Yogeeswari P, Sriram D. Bioorg. Med. Chem. Lett. 2005; 15: 4451
• 144 Bahl D, Athar F, Soares MB. P, de Sá MS, Moreira DR. M, Srivastava RM, Leite AC. L, Azam A. Bioorg. Med. Chem. 2010; 18: 6857
• 145 Borhade S, Tryambake P. Asian J. Chem. 2021; 33: 885
• 146 Parrilha GL, da Silva JG, Gouveia LF, Gasparoto AK, Dias RP, Rocha WR, Santos DA, Speziali NL, Beraldo H. Eur. J. Med. Chem. 2011; 46: 1473
• 147 de Araújo Neto LN, de Lima MC. A, de Oliveira JF, de Souza ER, Buonafina MD. S, Anjos MN. V, Brayner FA, Alves LC, Neves RP, Mendonça-Junior FJ. B. Chem.-Biol. Interact. 2017; 272: 172
• 148 Gomha SM, Abdelhady HA, Hassain DZ. H, Abdelmonsef AH, El-Naggar M, Elaasser MM, Mahmoud HK. Drug Des., Dev. Ther. 2021; 15: 659
• 149 Rodzi UL. M, Tajuddin AM, Sirat SS, Kamaruzaman NA, Meroshine NR, Anouar EH, Kassim K. Appl. Organomet. Chem. 2024; 38: e7306
• 150 Sibuh BZ, Gupta PK, Taneja P, Khanna S, Sarkar P, Pachisia S, Khan AA, Jha NK, Dua K, Singh SK, Pandey S, Slama P, Kesari KK, Roychoudhury S. Biomedicines 2021; 9: 1375
• 151 Daina A, Michielin O, Zoete V. Sci. Rep. 2017; 7: 42717
• 152 Nisha CM, Kumar A, Nair P, Gupta N, Silakari C, Tripathi T, Kumar A. Adv. Bioinform. 2016; 2016: 9258578
• 153 Mahanthesh M, Ranjith D, Yaligar R, Jyothi R, Narappa G, Ravi M. J. Pharmacogn. Phytochem. 2020; 9: 1799
• 154 Jain P, Vishvakarma VK, Singh P, Yadav S, Kumar R, Chandra S, Kumar D, Misra N. Chem. Biodiversity 2023; 20: e202300760
• 155 Farghaly TA, Abbas EM, Abd-Elghaffar HS, Elsayed MA, Elnaggar DH, El-Sayed AF, Abd-Elshafy DN, Mohamed SF. Sci. Rep. 2024; 14: 29378
• 156 Alam M, Abser MN, Kumer A, Bhuiyan MM. H, Akter P, Hossain ME, Chakma U. Heliyon 2023; 9: e16222
• 157 Ozturk II. J. Struct. Chem. 2023; 64: 743
• 158 Venkatraman R, Ameera H, Sitole L, Ellis E, Fronczek FR, Valente EJ. J. Chem. Crystallogr. 2009; 39: 711
• 159 Lobana TS, Butcher RJ. Transition Met. Chem. (Dordrecht, Neth.) 2004; 29: 291
• 160 Minh Quang N, Tran Thai H, Le Thi H, Duc Cuong N, Hien NQ, Hoang D, Ngoc VT. B, Ky Minh V, Van Tat P. ACS Omega 2023; 8: 11076
• 161 Khan M, Gohar H, Alam A, Wadood A, Shareef A, Ali M, Khalid A, Abdalla AN, Ullah F. ACS Omega 2023; 8: 5116
• 162 Leovac VM, Jovanović LS, Jevtović VS, Pelosi G, Bisceglie F. Polyhedron 2007; 26: 2971
• 163 Aly AA, Abdallah EM, Ahmed SA, Rabee MM, Bräse S. Molecules 2023; 28: 1808
• 164 Lobana TS, Bawa G, Butcher RJ, Liaw BJ, Liu CW. Polyhedron 2006; 25: 2897
• 165 Fuior A, Cebotari D, Garbuz O, Calancea S, Gulea A, Floquet S. Inorg. Chim. Acta 2023; 548: 121372
• 166 Ali MS, El-Saied FA, Shakdofa MM, Karnik S, Jaragh-Alhadad LA. J. Mol. Struct. 2023; 1274: 134485
• 167 Savir S, Wei ZJ, Liew JW. K, Vythilingam I, Lim YA. L, Saad HM, Sim KS, Tan KW. J. Mol. Struct. 2020; 1211: 128090
• 168 Jevtovic V, Alshamari AK, Milenković D, Dimitrić Marković J, Marković Z, Dimić D. Int. J. Mol. Sci. 2023; 24: 11910
• 169 Graur V, Chumakov Y, Garbuz O, Hureau C, Tsapkov V, Gulea A. Bioinorg. Chem. Appl. 2022; 2022: 2705332
• 170 Janjić GV, Jelić ST, Trišović NP, Popović DM, Dordević IS, Milčić MK. Cryst. Growth Des. 2020; 20: 2943
• 171 Ibrahim MM, El-Kemary MA, Al-Harbi SA, Al-Saidi HM, Sallam SA, Ramadan AE. M. M. J. Mol. Struct. 2021; 1228: 129706
• 172 Zhang YZ, Li HR, Dai J, Chen WJ, Zhang J, Liu Y. Biol. Trace Elem. Res. 2010; 135: 136
• 173 Yerragunta V, Kumaraswamy T, Suman D, Patil P, Samantha T. Pharmatutor Mag. 2013; 1: 54
• 174 Patil CB, Mahajan SK, Katti SA. J. Pharm. Sci. Res. 2009; 1: 11
• 175 Georgiou N, Katsogiannou A, Skourtis D, Iatrou H, Tzeli D, Vassiliou S, Javornik U, Plavec J, Mavromoustakos T. Molecules 2022; 27: 2537
• 176 Blumenkopf TA, Harrington JA, Koble CS, Bankston DD, Morrison RW, Bigham EC, Styles VL, Spector T. J. Med. Chem. 1992; 35: 2306
• 177 Zabin SA, Jejurkar CR. Asian J. Chem. 1995; 7: 542
• 178 Abu-Hussen AA. A, Emara AA. A. J. Coord. Chem. 2004; 57: 973
• 179 Manoj E, Kurup MR. P, Fun HK, Punnoose A. Polyhedron 2007; 26: 4451
• 180 Bacchi A, Carcelli M, Pelagatti P, Pelizzi C, Pelizzi G, Zani F. J. Inorg. Biochem. 1999; 75: 123
• 181 Chohan ZH, Pervez H, Khan KM, Supuran CT. J. Enzym. Inhib. Med. Chem. 2005; 20: 81
• 182 La Mendola D. Neural Regener. Res. 2020; 15: 665
• 183 Palanimuthu D, Poon R, Sahni S, Anjum R, Hibbs D, Lin H.-Y, Bernhardt PV, Kalinowski DS, Richardson DR. Eur. J. Med. Chem. 2017; 139: 612
• 184 Korkmaz G, Karaman I, Gezegen H. J. New Results Sci. 2024; 13: 61
• 185 Reshi ZA, Ahmad W, Lukatkin AS, Javed SB. Metabolites 2023; 13: 895
• 186 Rahim F, Ullah H, Taha M, Hussain R, Sarfaz M, Iqbal R, Iqbal N, Khan S, Ali Shah SA, Albalawi MA, Abdelaziz MA. Molecules 2023; 28: 21
• 187 Sagnou M, Mavroidi B, Kaminari A, Boukos N, Pelecanou M. ACS Chem. Neurosci. 2020; 11: 2266
• 188 Sousa G, de Almeida MC, Lócio LL, Santos VL. D, Bezerra DP, Silva VR, Almeida S, Simon A, Honório TD. S, Cabral LM, Castro RN. Pharmaceuticals 2022; 15: 1098
• 189 Altıntop MD, Temel HE, Sever B, Ciftçi GA, Kaplancıklı ZA. Molecules 2016; 21: 1598
• 190 Czylkowska A, Pitucha M, Raducka A, Fornal E, Kordialik-Bogacka E, Ścieszka S, Smoluch M, Burdan F, Jędrzejec M, Szymański P. Molecules 2025; 30: 129
• 191 Wijesinghe TP, Kaya B, Gonzálvez MA, Harmer JR, Gholam Azad M, Bernhardt PV, Dharmasivam M, Richardson DR. J. Med. Chem. 2023; 66: 15453
• 192 Kaya B, Gholam Azad M, Suleymanoglu M, Harmer JR, Wijesinghe TP, Richardson V, Zhao X, Bernhardt PV, Dharmasivam M, Richardson DR. J. Med. Chem. 2024; 67: 12155
• 193 Dharmasivam M, Kaya B, Wijesinghe T, Gholam Azad M, Gonzálvez MA, Hussaini M, Chekmarev J, Bernhardt PV. J. Med. Chem. 2023; 66: 1426
• 194 Kaya B, Smith H, Chen Y, Gholam Azad M, Russell TM, Richardson V, Dharmasivam M, Richardson DR. Inorg. Chem. 2024; 63: 20840
• 195 Donohoe MN, Upadhyay A, Pratt DA. J. Am. Chem. Soc. 2024; 146: 31307
• 196 Zhang H, Nazeeruddin MK, Choy WC. Adv. Mater. 2019; 31: 1805702
• 197 Arora S, Agarwal S, Singhal S. Int. J. Pharm. Pharm. Sci. 2014; 6: 34
• 198 Kumar B, Devi J, Dubey A, Tufail N, Khurana D. Appl. Organomet. Chem. 2024; 38: e7345
• 199 Verma KK, Nirwan N, Singh R, Bhojak N. J. Sci. Res. 2023; 15: 275 , https://doi.org/10.3390/inorganics11050195
• 200 Mahetar JG, Mamtora MJ, Gondaliya MB, Manawar RB, Shah MK. World J. Pharm. Res. 2014; 3: 4383
• 201 Ibrahim AA, Khaledi H, Hassandarvish P, Mohd Ali H, Karimian H. Dalton Trans. 2014; 43: 3850
• 202 Ahmed MF. A, Mahammadyunus V. Orient J. Chem. 2014; 30: 111
• 203 Manikandan R, Vijayan P, Anitha P, Prakash G, Viswanathamurthi P, Butcher RJ, Velmurugan K, Nandhakumar R. Inorg. Chim. Acta 2014; 421: 80
• 204 Li ZC, Chen LH, Yu XJ, Hu YH, Song KK, Zhou XW, Chen QX. J. Agric. Food Chem. 2010; 58: 12537
• 205 Verma K, Gupta P, Solanki K, Bhojak N. World J. Pharm. Pharm. Sci. 2015; 4: 1673
• 206 Khan T, Zehra S, Fatima U, Mishra N, Lawrence R, Maurya A, Singh S, Jeyakumar E, Raza S. Chem. Afr. 2023; 6: 1943
• 207 Ahmad MI, Veg E, Joshi S, Khan AR, Khan T. Russ. J. Gen. Chem. 2024; 94: 2470
• 208 Mildvan AS, Cohn M. J. Biol. Chem. 1966; 241: 1178
• 209 Rajarajeswari C, Ganeshpandian M, Palaniandavar M, Riyasdeen A, Akbarsha MA. J. Inorg. Biochem. 2014; 140: 255
• 210 Gubendran A, Rajesh J, Anitha K, Athappan P. J. Mol. Struct. 2014; 1075: 419
• 211 Veg E, Hashmi K, Ahmad MI, Joshi S, Khan AR, Khan T. Nat. Sci. 2025; 5: e70005
• 212 Li MX, Chen CL, Zhang D, Niu JY, Ji BS. Eur. J. Med. Chem. 2010; 45: 3169
• 213 Ahmed S, Jayathuna MA, Dharmasivam M, Bharathi S, Rahiman AK. Appl. Organomet. Chem. 2022; 36: e6782
• 214 Khan T, Ahmad R, Azad I, Raza S, Joshi S, Khan AR. Curr. Comput. Aided Drug Des. 2021; 17: 107
• 215 Khan T, Azad I, Ahmad R, Raza S, Dixit S, Joshi S, Khan AR. EXCLI J. 2018; 17: 331
• 216 Hashmi K, Rai S, Sharma S, Satya, Gupta S, Mishra P, Veg E, Khan T, Gupta A, Joshi S. Inorg. Chem. Commun. 2025; 174: 113967
• 217 Ramachandran E, Raja DS, Rath NP, Natarajan K. Inorg. Chem. 2013; 52: 1504
• 218 McCarthy CG. In The Chemistry of the Carbon–Nitrogen Bond . Patai S. John Wiley and Sons; New York: 1970: 392
• 219 Gálvez J, Guirado A. J. Comput. Chem. 2010; 31: 520
• 220 Bernhardt PV, Martínez M, Rodríguez C, Vázquez M. Dalton Trans. 2012; 41: 2122
• 221 Kalaivani P, Prabhakaran R, Ramachandran R, Dallemer F, Paramaguru G, Renganathan R, Poornima P, Vijaya Padma V, Natarajan K. Dalton Trans. 2012; 41: 2486
• 222 Khalilian MH, Mirzaeia S, Taherpour A. New J. Chem. 2015; 39: 9313
• 223 Raja DS, Paramaguru G, Bhuvanesh NS. P, Reibenspies JH, Renganathan R, Natarajan K. Dalton Trans. 2011; 40: 4548
• 224 Andres SA, Bajaj K, Vishnosky NS, Peterson MA, Mashuta MS, Buchanan RM, Bates PJ, Grapperhaus CA. Inorg. Chem. 2020; 59: 4924
• 225 Xie D, King TL, Banerjee A, Kohli V, Que EL. J. Am. Chem. Soc. 2016; 138: 2937
• 226 Anjum R, Palanimuthu D, Kalinowski DS, Lewis W, Park KC, Kovacevic Z, Khan IU, Richardson DR. Inorg. Chem. 2019; 58: 13709
• 227 Cater MA, Pearson HB, Wolyniec K, Klaver P, Bilandzic M, Paterson BM, Bush AI, Humbert PO, La Fontaine S, Donnelly PS, Haupt Y. ACS Chem. Biol. 2013; 8: 1621
• 228 French FA, Freedlander BL. Cancer Res. 1958; 18: 1290
• 229 Koçyiğit ÜM, Doğan M, Muğlu H, Taslimi P, Tüzün B, Yakan H, Bal H, Güzel E, Gülçin İ. J. Mol. Struct. 2022; 1264: 133249
• 230 Kudličková Z, Michalková R, Salayová A, Ksiažek M, Vilková M, Bekešová S, Mojžiš J. Molecules 2023; 28: 6583
• 231 Badiger J, Manjulatha K, Girish M, Sharif A, Purohit MG. ARKIVOC 2009; (xii): 217
• 232 Taha M, Imran S, Salahuddin M, Iqbal N, Rahim F, Uddin N, Shehzad A, Farooq RK, Alomari M, Khan KM. Bioorg. Chem. 2021; 110: 104808
• 233 Batool Z, Ullah S, Khan A, Mali SN, Gurav SS, Jawarkar RD, Alshammari A, Albekairi NA, Al-Harrasi A, Shafiq Z. Sci. Rep. 2024; 14: 25754
• 234 Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Adv. Drug Delivery Rev. 2012; 64: 4
• 235 Ammar YA, Ragab A, Migahed MA, Al-Sharbasy S, Salem MA, Riad OK. M, Selim HM. R. M, Abd-Elmaksoud GA, Abusaif MS. RSC Adv. 2023; 13: 27363
• 236 Erin N, Grahovac J, Brozovic A, Efferth T. Drug Resistance Updates 2020; 53: 100715
• 237 Mele L, Del Vecchio V, Liccardo D, Prisco C, Schwerdtfeger M, Robinson N, Desiderio V, Tirino V, Papaccio G, La Noce M. Cancer Treat. Rev. 2020; 88: 102043
• 238 Azad I. Ahmad R. Khan T. Saquib M. Hassan F. Akhter Y. Khan AR. Nasibullah M. Fut. med. chem.. 2020
• 239 Wu Z, Ramsundar B, Feinberg EN, Gomes J, Geniesse C, Pappu AS, Leswing K, Pande V. Chem. Sci. 2018; 9: 513
• 240 Li Q, Kang C. Int. J. Mol. Sci. 2020; 21: 5262
• 241 Nguyen HM, Quang NM. Hue Univ. J. Sci.: Nat. Sci. 2024; 133: 5
• 242 Stewart JJ. J. Mol. Model. 2013; 19: 1
• 243 Al-Busaidi IJ, Haque A, Al Rasbi NK, Khan MS. Synth. Met. 2019; 257: 116189
• 244 Huang L, Feng ZL, Wang YT, Lin LG. Chin. J. Nat. Med. 2017; 15: 881
• 245 Quang NM, Mau TX, Nhung NT. A, An TN. M, Van Tat P. J. Mol. Struct. 2019; 1195: 95
• 246 Acharya PT, Bhavsar ZA, Jethava DJ, Patel DB, Patel HD. J. Mol. Struct. 2021; 1226: 129268
• 247 Matesanz AI, Souza P. Mini-Rev. Med. Chem. 2009; 9: 1389
• 248 Ahmed MF, Almalki AH. Arab. J. Chem. 2021; 14: 102989
• 249 Liew SK, Malagobadan S, Arshad NM, Nagoor NH. Biomolecules 2020; 10: 138
• 250 Song J, Pan R, Li G, Su W, Song X, Li J, Liu S. Med. Chem. Res. 2020; 29: 630
• 251 Wolohan P, Yoo J, Welch MJ, Reichert DE. J. Med. Chem. 2005; 48: 5561
• 252 Sripathi MP, Berely S, Ramana Reddy CV. Heteroat. Chem. 2019; 2019: 3507837
• 253 Umamatheswari S, Balaji B, Ramanathan M, Kabilan S. Eur. J. Med. Chem. 2011; 46: 1415
• 254 Serda M, Mrozek-Wilczkiewicz A, Jampilek J, Pesko M, Kralova K, Vejsova M, Musiol R, Ratuszna A, Polanski J. Molecules 2012; 17: 13483
• 255 Anzenbacherová E, Janalík J, Popa I, Strnad M, Anzenbacher P. Biomed. Pap. Palacky Univ. Olomouc 2005; 149: 349
• 256 Kanayama N, Kanari C, Masuda Y, Ohmori S, Ooie T. Xenobiotica 2007; 37: 139
• 257 Glaeser H, Bailey DG, Dresser GK, Gregor JC, Schwarz UI, McGrath JS, Jolicoeur E, Lee W, Leake BF, Tirona RG, Kim RB. Clin. Pharm. Ther. 2007; 81: 362
• 258 Süleymanoğlu M, Erdem-Kuruca S, Bal-Demirci T, Özdemir N, Ülküseven B, Yaylım İ. J. Biochem. Mol. Toxicol. 2020; 34: e22512
• 259 Jacob ÍT, Gomes FO, de Miranda MD, de Almeida SM, da Cruz-Filho IJ, Peixoto CA, da Silva TG, Moreira DR, de Melo CM, de Oliveira JF, de Lima MC. Pharmacol. Rep. 2021; 73: 907
• 260 Siddiqui B, Yadav CS, Akil M, Faiyyaz M, Khan AR, Ahmad N, Hassan F, Azad MI, Owais M, Nasibullah M, Azad I. Comb. Chem. High Throughput Screening 2025; 10: e202401807
• 261 Manathunga M, Götz AW, Merz KM. Jr. Curr. Opin. Struct. Biol. 2022; 75: 102417
• 262 Sharma V, Wakode S, Kumar H. Structure- and Ligand-Based Drug Design: Concepts, Approaches, and Challenges. In Chemoinformatics and Bioinformatics in the Pharmaceutical Sciences. Sharma N, Ojha H, Raghav PK, Goyal RK. Academic Press/Elsevier; London: 2021: 27-53
• 263 Han R, Yoon H, Kim G, Lee H, Lee Y. Pharmaceuticals 2023; 16: 1259
• 264 Azad I, Khan T, Maurya AK, Azad MI, Mishra N, Alanazi AM. J. Mol. Recognit. 2021; 34: e2918