Author(s):
Ronak Patadiya, Sangita Shukla, Nikunj Patadiya
Email(s):
nikunj20899@gmail.com
DOI:
10.52711/0974-4150.2025.00058 
Address:
Ronak Patadiya1, Sangita Shukla1, Nikunj Patadiya2*
1Department of Pharmacognosy, Indubhai Patel College of Pharmacy and Research Centre, Dharmaj, Gujarat, India.
2Research Scholar, Gujarat Technological University, Ahmedabad, Gujarat, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 6,
Year - 2025
ABSTRACT:
Tuberculosis (TB) remains a major global health concern, especially with the rise of drug-resistant strains. The InhA enzyme, which is essential for the cell wall formation of Mycobacterium tuberculosis, has become an important target for new drug discovery. In this review, studies from the last few years are summarized, focusing on about 26 newly developed InhA inhibitors. These compounds feature a variety of effective ring systems—including imidazoquinolines, coumarin-thiazoles, pyrrole-pyrimidines, thienopyridinones, oxadiazoles, and molecular hybrids—that play a key role in their antimycobacterial activity. Among them, three molecules 5a, NITD-916, and 3g showed the strongest activity, with the lowest MIC (minimum inhibitory concentration) Value. These findings highlight the progress made in recent years and point to new promising leads for the development of future anti- tubercular agents.
Cite this article:
Ronak Patadiya, Sangita Shukla, Nikunj Patadiya. Targeting InhA in Mycobacterium Tuberculosis: Recent Advances and Novel Scaffolds. Asian Journal of Research in Chemistry. 2025; 18(6):378-4. doi: 10.52711/0974-4150.2025.00058
Cite(Electronic):
Ronak Patadiya, Sangita Shukla, Nikunj Patadiya. Targeting InhA in Mycobacterium Tuberculosis: Recent Advances and Novel Scaffolds. Asian Journal of Research in Chemistry. 2025; 18(6):378-4. doi: 10.52711/0974-4150.2025.00058 Available on: https://www.ajrconline.org/AbstractView.aspx?PID=2025-18-6-3
REFERENCES:
1. Shah H, Patel J, Rai S, Sen A. Advancing tuberculosis elimination in India: A qualitative review of current strategies and areas for improvement in tuberculosis preventive treatment. IJID Reg. 2025: 100556. doi: 10.1016/j.ijregi.
2. Juliet A, Dave P, Marilyn M, Courtney L, Gillian T, David BA. Living with tuberculosis: a qualitative study of patients’ experiences with disease and treatment. BMC Public Health. 2022; 22(1): 1717. https://doi.org/10.1186/s12889-022-14115-7.
3. Salla AM, Simon AL, Helen JS, Mark EE. Atle F, Jimmy V. Patient adherence to tuberculosis treatment: a systematic review of qualitative research. PLoS Med. 2007; 4(7): e238. https://doi.org/10.1371/journal.pmed.0040238 PMID: 17676945
4. Munita JM, Arias CA. Mechanisms of Antibiotic Resistance. Microbiol Spectr. 2016; 4(2): 10. 10.1128/microbiolspec.VMBF-0016-2015
5. Patadiya N, Panchal N, Vaghela V. A review on enzyme inhibitors. Int. Res. J. Pharm. 2021; 12(6): 60-66. 10.7897/2230-8407.1206145
6. Patadiya N, Vaghela V. Design, in-silico ADME Study and molecular docking study of novel quinoline-4-on derivatives as Factor Xa Inhibitor as Potential anti-coagulating agents. Asian Journal of Pharmaceutical Research. 2022; 12(3): 207-11. 10.52711/2231-5691.2022.00034
7. Dumpala RL, Patel J, Patadiya N, Patil C. Solubility and dissolution enhancement of Erlotinib by liquisolid compact technique. International Journal of Pharma. 2020; 2(4): 271-90.
8. World Health Organization. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva: World Health Organization; 2018. Available from: https://www.who.int/publications/i/item/9789241550239. Access on 15th September 2025
9. Patadiya N, Dumpala R. A high-profile review on new oral clotting factor Xa inhibitor: betrixaban. Eur J Pharm Med Res. 2021; 8(1): 239-47.
10. Daniel TM. The history of tuberculosis. Respir Med. 2006; 100(11): 1862–70. doi: 10.1016/j.rmed.2006.08.006
11. Patel R, Darji J, Patadiya N, Thummar M. Development and evaluation of medicated chewing gum of raloxifene hydrochloride. International Journal of Pharmaceutical and Biological Science Archive. 2021; 9(3): 1-12.
12. Daniel TM, Bates JH, Downes KA. History of tuberculosis. In: Bloom BR, editor. Tuberculosis: Pathogenesis, Protection, and Control. Washington, DC: ASM Press; 1994. p. 13-35. doi:10.1128/9781555818357.
13. Patadiya N. Steroids: classification, nomenculture and stereochemistry. International Journal of Universal Pharmacy and Bio Sciences. 2020; 9(5): 28-38.
14. Makvana P, Patadiya N, Baria D. Design, molecular docking, in-silico admet prediction, synthesis and evaluation of novel quinazoline derivatives as factor XA inhibitors. Int. Res. J. Pharm. 2022; 13(3): 30-7. http://dx.doi.org/10.7897/2230- 8407.1303187
15. Chang CC, Crane M, Zhou J, Mina M, Post JJ, Cameron BA, et al. HIV and co-infections. Immunol Rev. 2013; 254(1): 114-42. doi:10.1111/imr.12063.
16. Patadiya N, Vaghela V. An efficient method for synthesis of flavanone. Asian J. Pharm. Res. 2022; 12(3): 221-224. doi: 10.52711/2231-5691.2022.00039
17. Kolekar T, Patadiya N. Self-emulsifying drug delivery Systems (SEDDS): A novel dissolution enhancement technique. International Journal of Trend in Innovative Research. 2020; 2(5): 10-20.
18. Maison DP. Tuberculosis pathophysiology and anti-VEGF intervention. J Clin Tuberc Other Mycobact Dis. 2022; 27: 100300. doi: 10.1016/j.jctube.2022.100300.
19. Soni D, Patadiya N. A wonderful hormone: estrogen. International Journal of Pharma. 2020; 2(5): 362-8.
20. Patadiya N, Vaghela V. A novel and ecofriendly method for synthesis of 3- benzylidene-2-phenylchroman-4-one analogs. Asian J. Research Chem. June 2022; 15(3): 195-199. doi: 10.52711/0974- 4150.2022.00033.
21. Patadiya N, Vaghela V. An optimized method for synthesis of 2’hydroxy chalcone. Asian J. Research Chem. 2022; 15(3): 210-212. doi: 10.52711/0974-4150.2022.00036
22. Kolekar T, Patadiya N. Dissolution enhancement technique: self-emulsifying drug delivery systems (SEDDS). International Journal of Institutional Pharmacy and Life Sciences. 2020; 10(6): 25-39.
23. Patel S, Patadiya N, Patel A. Formulation and Evaluation of Turmeric and Coriander Based Herbal Nail Polishes. Int. J. of Pharm. Sci. 2024;2(2):488-95. 10.5281/zenodo.10679282
24. Dartois VA, Rubin EJ. Anti-tuberculosis treatment strategies and drug development: challenges and priorities. Nat Rev Microbiol. 2022; 20(11): 685-701. doi:10.1038/s41579-022-00731-y.
25. Parikh SL, Xiao G, Tonge PJ. Inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis, by triclosan and isoniazid. Biochemistry. 2000; 39(26): 7645–50. doi:10.1021/bi0008940.
26. Rožman K, Sosič I, Fernandez R, Young RJ, Mendoza A, Gobec S, et al. A new “golden age” for the antitubercular target InhA. Drug Discov Today. 2017; 22(3): 492–502. doi: 10.1016/j.drudis.2016.09.009.
27. Ardiansah B. Chalcones bearing N, O, and S-heterocycles: recent notes on their biological significance. J Appl Pharm Sci. 2019; 9(8): 117–29. doi:10.7324/JAPS.2019.90816.
28. Kaur H, Singh L, Chibale K, Singh K. Structure elaboration of isoniazid: synthesis, in silico molecular docking and antimycobacterial activity of isoniazid–pyrimidine conjugates. Mol Divers. 2020; 24(4): 949 doi:10.1007/s11030-019-10004-1.
29. Chinnamulagund S, Joshi AS, Avunoori S, Kulkarni VH, Joshi SD, Joshi CD. Synthesis and antitubercular evaluation of certain pyrrole derivatives. Indo Am J Pharm Res. 2023; 13(3). doi:10.5281/zenodo.7755252.
30. Deidda D, Lampis G, Fioravanti R, Biava M, Porretta GC, Zanetti S, et al. Bactericidal activities of the pyrrole derivative BM212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains. Antimicrob Agents Chemother. 1998; 42(11): 3035–7. doi:10.1128/AAC.42.11.3035.
31. Yogesh MK, Adinarayana N, Singarapalle S, Muthyala MKK, Ala C, Shankaranarayanan M, Kondapalli VGCS. Design, synthesis, and anti-mycobacterial evaluation of 1,8-naphthyridine-3-carbonitrile analogues. RSC Adv. 2024; 14(34): 22676–89. doi:10.1039/d4ra04262j.
32. Ravallika A, Aishwarya N, Jyothi K, Dharmarajan S, Pralok KS, Aditi G, Krishnan R. Synthesis, characterization, and anti-TB application of redox-active ethyl carbazate-derivatized phenanthroline and its silver complexes. ACS Omega. 2025; 10(27): 28993–29013. doi:10.1021/acsomega.5c00871.
33. Khetmalis YM, Chitti S, Wunnava AU, Kumar BK, Kumar MMK, Murugesan S, Sekhar KVGC. Design, synthesis and anti-mycobacterial evaluation of imidazo[1,2-a] pyridine analogues. RSC Med Chem. 2022; 13: 327–42. doi:10.1039/D1MD00367D.
34. Dingiş Birgül Sİ, Kumari J, Tamhaev R, Mourey L, Lherbet C, Sriram D, Küçükgüzel İ. In silico design, synthesis and antitubercular activity of novel 2-acylhydrazono-5-arylmethylene-4-thiazolidinones as enoyl- acyl carrier protein reductase inhibitors. J Biomol Struct Dyn. 2024; 1–19. doi:10.1080/07391102.2024.2319678.
35. Emeline G, Hikmat A, Frédéric R, Christian L, Rasoul T, Mélina C, Hikmat A, Deborah R, Giulia D, Maria R, Laurent M, Lionel M. Exploring the plasticity of the InhA substrate-binding site using new diaryl ether inhibitors. J Med Chem. 2024; Advance online publication. doi: 10.1016/j.bioorg.2023.107032.
36. Manjunatha UH, Rao SPS, Kondreddi RR, Noble CG, Camacho LR, Tan BH, Ng SH, Ng PS, Ma NL, Lakshminarayana SB, Herve M, Barnes SW, Yu W, Kuhen K, Blasco F, Beer D, Walker JR, Tonge PJ, Glynne R, Smith PW, Diagana TT. Direct inhibitors of InhA are active against Mycobacterium tuberculosis. Sci Transl Med. 2015; 7(269): 269ra3. doi:10.1126/scitranslmed.3010597.
37. Kassem AF, Sabt A, Korycka-Machala M, Shaldam MA, Kawka M, Dziadek B, Kuzioła M, Dziadek J, Batran RZ. New coumarin linked thiazole derivatives as antimycobacterial agents: Design, synthesis, enoyl acyl carrier protein reductase (InhA) inhibition and molecular modeling. Bioorg Chem. 2024; 150: 107511. doi: 10.1016/j.bioorg.2024.107511.
38. Pflégr V, Maixnerová J, Stolaříková J, Pál A, Korduláková J, Trejtnar F, Vinšová J, Krátký M. Design and synthesis of highly active antimycobacterial mutual esters of 2-(2-isonicotinoylhydrazineylidene) propanoic acid. Pharmaceuticals (Basel). 2021; 14(12): 1302. doi:10.3390/ph14121302.
39. Rasha ZB, Ahmed S, Jarosław D, Asmaa FK. Design, synthesis and computational studies of new azaheterocyclic coumarin derivatives as anti-Mycobacterium tuberculosis agents targeting enoyl acyl carrier protein reductase (InhA). Eur J Med Chem. 2014; 82: 377–88. doi: 10.1016/j.ejmech.2014.06.013.
40. Vinay KK, Yadav D, Bodke, Shivakumar N, Udayakumar D. Synthesis, characterization, computational, and photophysical investigation of novel pyran-azo bridged benzothiazoles and their biological studies. ChemistrySelect. 2025; 10(13): e202404988. doi:10.1002/slct.202404988.
41. Singh D, Parkali PM, Hani U, Osmani RAM, Haider N, Kumari J, Sriram D, Lherbet C, Siddappa BCR, Dixit SR. Structure-based design, synthesis, computational screening and biological evaluation of novel pyrrole fused pyrimidine derivatives targeting InhA enzyme. RSC Adv. 2025; 15(32): 25776-25798. doi:10.1039/D5RA03004H.
42. Hoffmann P, Azéma-Despeyroux J, Goncalves F, Stamilla A, Saffon-Merceron N, Rodriguez F, Degiacomi G, Pasca MR, Lherbet C. Imidazoquinoline derivatives as potential inhibitors of InhA enzyme and Mycobacterium tuberculosis. Molecules. 2024; 29(13): 3076. doi:10.3390/molecules29133076.
43. Enas AT, Farghaly AO, Nadia MM, Yasser MI, Ahmed MA. Design, synthesis, and biological activity profiling study of imidazolinone-based hydrazones as potential multitarget antimycobacterial agents. Bioorg Chem. 2018; 81: 525–34. doi: 10.1016/j.bioorg.2018.09.016.
44. Martina HR, Nina G, Rok F, Izidor S, Aljoša B, Jakob K, Martin J, Stanislav G, Stane P. Development and evaluation of novel InhA inhibitors inspired by thiadiazole and tetrahydropyran series of inhibitors. Acta Pharm. 2025; 75: 185–218. doi:10.2478/acph-2025-0016.
45. Mahnashi MH, Ramachandraiah PKS, Al Awadh AA, Almazni IA, Asiri YI, Shaikh IA, Mannasaheb BA, Avunoori S, Khan AA, Joshi SD. Design, synthesis and in silico molecular modelling studies of 2- hydrazineyl-2-oxoethyl-4-(1H-pyrrol-1-yl) benzoate derivatives: potent dual DHFR and ENR-reductase inhibitors with antitubercular, antibacterial and cytotoxic potential. PLoS One. 2025; 20(5): e0323702. doi: 10.1371/journal.pone.0323702.
46. Kendre BV, Hardas PS, Pat RC, Kendre RB, Landge MG, Bhusare SR. Design, synthesis and biological evaluation of chromone fused 1,3,4-thiadiazoles as highly potent nontoxic inhibitors of enoyl-acyl carrier proteins in M. tuberculosis. Int J New Chem. 2025; 12(4): 581–606. doi:10.22034/ijnc.2024.2020026.1369.
47. Patel T, Chauhan N, Bhatt VD, Bhatt BS. Design and synthesis of novel imidazolidine-2,4-dione derivatives as InhA inhibitors: spectral characterization, computational, and biological studies. Mater Today Proc. 2022; 57(1): 217–23. doi: 10.1016/j.matpr.2022.02.364.
48. Ahmed S, Maha-Hamadien A, Ebaid MS, Pawełczyk J, Abd El Salam HA, Son NT, Ha NX, Vaali MMA, Traiki T, Elsawi AE, Dziadek B, Dziadek J, Eldehna WM. Identification of 2-(N-aryl-1,2,3-triazol-4- yl) quinoline derivatives as antitubercular agents endowed with InhA inhibitory activity. Front Chem. 2024; 12:1424017. doi:10.3389/fchem.2024.1424017
49. Liang L, Liu Z, Chen J, Zha Q, Zhou Y, Li J, Hu Y, Chen X, Zhang T, Zhang N. Design and synthesis of Thieno[3,2-b] pyridine derivatives exhibiting potent activities against Mycobacterium tuberculosis in vivo by targeting Enoyl-ACP reductase. Eur J Med Chem. 2024; 279: 116806. doi: 10.1016/j.ejmech.2024.116806
50. Kumar P, Malik P, Ali J, Saxena D, Singampalli A, Bandela R, et al. Exploration of pyrazole-based pyridine-4-carbohydrazide derivatives as drug-resistant M. tuberculosis agents: design, synthesis, biological evaluation, and in-silico studies. J Enzyme Inhib Med Chem. 2025; 40(1): 1391–405. doi:10.1080/17568919.2025.2525069.
51. Reddy BRS, Babu KS, Mulakayala N, Gajulapalli VPR. Synthesis of novel 5-oxo-1,2,4-oxadiazole derivatives as antitubercular agents and their molecular docking study toward enoyl reductase (InhA) enzyme. ChemSelect. 2023; 8(4): e202204093. doi:10.1002/slct.202204093
52. Patel VP, Tripathi RKP, Mandal SD. Synthesis, biological evaluation, molecular docking studies and ADMET prediction of oxindole-based hybrids for the treatment of tuberculosis. Curr Comput Aided Drug Des. 2025; 21(4): 517–33. doi:10.2174/0115734099353857241022102426
53. Wael S, Norah AA, Basant F, Marwa MA, Shaker Y, Sherin ME, Samar E, Nermine AO. Synthesis, in vitro and in silico molecular docking studies of novel phthalimide–pyrimidine hybrid analogues to thalidomide as potent antitubercular agents. SynOpen. 2024; 9: 73–83. doi:10.1055/s-0043-1775424.
54. Prem Kumar SR, Shaikh IA, Mahnashi MH, Alshahrani MA, Dixit SR, Kulkarni VH, Lherbet C, Gadad AK, Aminabhavi TM, Joshi SD. Design, synthesis and computational approach to study novel pyrrole scaffolds as active inhibitors of enoyl ACP reductase (InhA) and Mycobacterium tuberculosis antagonists. J Indian Chem Soc. 2022; 99(11): 100674. doi: 10.1016/j.jics.2022.100674
55. Kumar G, Seboletswe P, Mishra S, Manhas N, Ghumran S, Kerru N, Roquet-Banères F, Foubert M, Kremer L, Bhargava G, Singh P. Isoniazid-dihydropyrimidinone molecular hybrids: Design, synthesis, antitubercular activity, and cytotoxicity investigations with computational validation. ChemMedChem. 2025; 20(11). doi:10.1002/cmdc.
56. Kusurkar RV, Rayani RH, Parmar DR, Bhoi MN, Zunjar VH, Soni JY. Design, synthesis, in-silico ADME prediction, molecular docking and antitubercular screening of bromo-pyridyl tethered 3-chloro-2- azetidinone derivatives. Results Chem. 2022; 4: 100357. doi: 10.1016/j.rechem.
57. Patel S, Patadiya N. Preparation and Standardization of Ayurvedic Nindra Vati. Int. J. of Pharm. Sci. 2024; 2(2): 403-9. 10.5281/zenodo.10673390
58. Dalvi D, Patel P, Dalvi H, Patel S, Patadiya N. Preparation and evaluation of herbal hair spray. Int. J. of Pharm. Sci. 2024; 2(8): 3652-9. 10.5281/zenodo.13367155
59. Nikunj P, Shilpa P, Pooja M, Rikin P. Preparation and standardization of chitrakadi vati. J Pharm Sci Innov. 2022; 11(3): 28-35. http://dx.doi.org/10.7897/2277- 4572.113230.
60. Patel Y, Patel T, Patel S, Patel S, Patadiya N. Preparation and evaluation of herbal tooth powder using herbal resources. International Journal of Pharmacognosy and Pharmaceutic al Sciences. 2024; 6(2): 60-3. https://dx.doi.org/10.33545/27067009.2024.v6.i2a.159
61. Patel R, Rathod D, Shah N, Vaghela V, Patadiya N. Inhibitors as a therapeutic frontier in lung cancer: Mechanism, opportunities, and molecular docking studies. Computers in Biology and Medicine. 2025 Sep 1; 196:110889. https://doi.org/10.1016/j.compbiomed.2025.110889
62. Patadiya N, Teli A, Kazi S, Rathod P, Patel S. Preparation and evaluation of herbal mosquito repellent gel. International Journal of Pharmaceutical Research and Applications. 2025; 10(3): 1915-1921. 10.35629/4494-100319151921
63. J Joshi, B Vala, S Singh, S Patel, N Patadiya. A Review on Natural Molecules as Pancreatic Lipase Inhibitor. Research Journal of Pharmacognosy and Phytochemistry. 2025; 17(2): 116-122. 10.52711/0975-4385.2025.00020
64. Hiren R, Richa D, Nikunj P. a Validated, Fast and Simple, Simultaneous Determination of Captopril and Telmisartan in Laboratory Prepared Mixture for Use in Haemodialysis Patients Suffering from Inflammation. International Journal of Pharmaceutical Quality Assurance 2023; 14(2): 255-261.
65. Nikunj P. Steroids: classification, nomenclature and stereochemistry. International Journal of Universal Pharmacy and Bio Sciences. 2020; 9(5): 28-38
66. Hetvi R, Misba V, Aman V, Shilpa P, Nikunj P. Preparation and standardization of Ayurvedic Triphala-Guggul Vati. International Journal of Pharmacy and Pharmaceutical Science 2025; 7(1): 135-139. https://www.doi.org/10.33545/26647222.2025.v7.i1b.162
67. Aman V, Hetvi R, Misba V, Shilpa P, Nikunj P. Method Development for Quantification of Gallic Acid in Triphala Guggulu Vati. International Journal of Pharmaceutical Research and Development 2025; 7(1): 312-318. https://doi.org/10.33545/26646862.2025.v7.i1
68. Patadiya N, Vaghela V, Padhra Saurav. Optimisation of synthetic condition for 2’hydroxy Chalcone by using mixture design. Asian J. Research Chem. 2023; 16(6): 417- 422. doi: 10.52711/0974-4150.2023.00068.
69. Unissa AN, Subbian S, Hanna LE, Selvakumar N. Overview on mechanisms of isoniazid action and resistance in Mycobacterium tuberculosis. Infect Genet Evol. 2016; 45: 474–92. doi: 10.1016/j.meegid.2016.09.004.