Volume-12, Issue-6, June 2026

Abstract

The synthesis of oxothiazolidinyl-phenothiazinone derivatives was carried out starting from the condensation of resorcinol and acetoacetic ester, which gives coumarin. Simultaneously, synthesis of cyclic thiazolidin-4-one was done by condensation of aromatic substituted/unsubstituted aldehyde-benzidine and aromatic substituted/unsubstituted aldehyde-benzene-1,4-diamine with thioglycollic acid in the presence of ZnCl₂ in trace amounts. Subsequently, substituted-amine reacted with coumarin in the presence of ZnCl₂ to yield amino-thiazolidin-4-one, and further cyclization took place. The final phenothiazinone heterocycles were synthesized in the presence of sulfur powder and iodine. The structures of the novel synthesized derivatives were established by elemental analysis, UV, FT-IR, ¹H-NMR, and mass spectra. The obtained derivatives exhibited excellent to moderate antibacterial and antifungal activity.  

Keywords: Acetoacetic ester, coumarin, benzidine, benzene-1,4-diamine, thioglycollic acid, aromatic substituted/unsubstituted aldehyde.

References

[1] Qiu L, Chen W, Wang J, Deng X, Liu H & Qiu J, Front Immunol, 16 (2025) 1712724. 
[2] Al Zahrani N A, Al-Ghamdi H A & El-Shishtawy R M, J Mol Struct, 1324 (2025) 140885. 
[3] Ronco T, Juul M, Reynier Z, Christensen J B, Svenningsen S & Olsen R H, Indian J Microbiol, 64 (2024) 743. 
[4] Morak M, Odawska B, Jelen M & Pluta K, Pol Merk Lek, 159 (2009) 671. 
[5] Krystian P, Małgorzata J, Beata M, Micha Z, Jolanta A & Maja K, Pharmacol Rep, 62 (2010) 319. 
[6] Weiss E A, Tauber M J, Kelley R F, Ahrens M J, Ratner M A & Wasielewski M R, J Am Chem Soc, 127 (2005) 11842. 
[7] Lai R Y, Kong X, Jenekhe S A & Bard A J, J Am Chem Soc, 125 (2003) 12631. 
[8] Rhee H W, Choi S J, Yoo S H, Jang Y O, Park H H, Pinto R M, Cameselle J C, Sandoval F J, Roje S, Han K, Chung D S, Suh J & Hong J I, J Am Chem Soc, 131 (2009) 10107. 
[9] Ito T, Kondo A, Terada S & Nishimoto S, J Am Chem Soc, 128 (2006) 10934. 
[10] Kalwania G S, Chomal S, Choudhary S, Shyam R & Kumari S, Orient J Chem, 28 (2012) 1. 
[11] Bayoumy N M, Fadda A A, Gaffer H E & Soliman N N, Sci Rep, 16 (2026) 10592. 
[12] Kenia H et al., IOSR J Pharm, 10 (2020) 54. 
[13] Singh S K, Nath G, Kumar A & Sellamuthu S K, Anti Infect Agents, 17 (2019) 50. 
[14] Wainwright M & Amaral L, Trop Med Int Health, 10 (2005) 501. 
[15] Spengler G, Csonka Á, Molnar J & Amaral L, Anticancer Res, 36 (2016) 5701. 
[16] Venkatesan K, Satyanarayana V S V & Sivakumar A, Polycycl Aromat Compd, 43 (2023) 850. 
[17] Marinov M, Nikolova I, Kostova I & Stoyanov N, Phosphorus Sulfur Silicon Relat Elem, 197 (2022) 128. 
[18] Venkatesan K, Satyanarayana V S V, Mohanapriya K, Khora S S & Sivakumar A, Res Chem Intermed, 45 (2015) 595. 
[19] Jadvani V V, Makwana B M & Naliapara Y T, Indian J Chem, 65 (2026) 306. 
[20] Metwally N H, Radwan I T, El-Serwy W S & Mohamed M A, Bioorg Chem, 84 (2019) 456. 
[21] Gharge S, Alegaon S G, Ranade S D, Khatib N A, Kavalapure R S, Prashantha Kumar B R, Vinod D & Bavage N B, Eur J Med Chem Rep, 11 (2024) 100151. 
[22] Saeed A, Al-Masoudi N A & Latif M, Arch Pharm Chem Life Sci, 346 (2013) 1. 
[23] Alshammari M B, Aly A A, Youssif B G M, Bräse S, Ahmad A, Brown A B, Ibrahim M A A & Mohamed A H, Front Chem, 10 (2022) 1. 
[24] Chaban T, Matiichuk Y, Chulovska Z, Tymoshuk O, Chaban I & Matiychuk V, Arch Pharm, 354 (2021) 2100037. 
[25] Klenc J, Raux E, Barnes S, Sullivan S, Duszynska B, Bojarski A & Strekowski L, J Heterocycl Chem, 46 (2009) 259. 
[26] Jacques C, Bacqueville D, Jeanjean-Miquel C, Génies C, Noizet M, Tourette A, Bessou-Touya S & Duplan H, Int J Cosmet Sci, 43 (2021) 391. 
[27] Abd El-Karim S S, Mohamed H S, Abdelhameed M F, Amr A E-G E, Almehizia A A & Nossier E S, Bioorg Chem, 111 (2021) 104827. 
[28] Havrylyuk D, Zimenkovsky B, Karpenko O, Grellier P & Lesyk R, Eur J Med Chem, 85 (2014) 245. 
[29] Nitsche C, Schreier V N, Behnam M A M, Kumar A, Bartenschlager R & Klein C D, J Med Chem, 56 (2013) 8389. 
[30] Patel N B & Patel M D, Med Chem Res, 26 (2017) 1772. 
[31] Iqbal M A, Husain A, Alam O, Khan S A, Ahmad A, Haider M R & Alam M A, Arch Pharm, 353 (2020) 2000071. 
[32] Tratrat C, Petrou A, Geronikaki A, Ivanov M, Kostić M, Soković M, Vizirianakis I S, Theodoroula N F & Haroun M, Molecules, 27 (2022) 1930. 
[33] Ozen C, Unlusoy M C, Aliary N, Ozturk M & Dundar O B, J Pharm Sci, 20 (2017) 415. 
[34] Asati V & Bharti S K, J Mol Struct, 1154 (2018) 406. 
[35] Pavase L S & Mane D V, Chem Biol Interact, 7 (2017) 183. 
[36] Liu K, Rao W, Parikh H, Li Q, Guo T, Grant S, Kellogg G & Zhang S, Eur J Med Chem, 47 (2012) 125. 
[37] Sharma P, Reddy T S, Kumar N P, Senwar K R, Bhargava S K & Shankaraiah N, Eur J Med Chem, 138 (2017) 234. 
[38] Datar P A & Aher S B, J Saudi Chem Soc, 20 (2016) 196. 
[39] Shrivastava S K, Batham A, Sinha S K, Parida T K, Garabadu D & Choubey P K, Med Chem Res, 25 (2016) 2258. 
[40] Sharma R K, Younis Y, Mugumbate G, Njoroge M, Gut J, Rosenthal P J & Chibale K, Eur J Med Chem, 90 (2015) 507. 

Abstract

Preformulation studies are essential for establishing the physicochemical and biopharmaceutical characteristics of novel therapeutic candidates before formulation development. The present investigation focuses on the systematic preformulation evaluation of FP-1 peptide, a promising bioactive compound with potential neuroprotective applications. The study aimed to assess key parameters influencing its stability, compatibility, and suitability for drug delivery. 
FP-1 peptide was characterized for its organoleptic properties, solubility profile, and pH-dependent stability. The peptide exhibited good solubility in aqueous media with optimal stability observed within a neutral to slightly acidic pH range. Partition coefficient analysis indicated its hydrophilic nature, suggesting challenges in passive membrane permeability. Thermal behavior and crystallinity were evaluated using differential scanning calorimetry (DSC) and X-ray diffraction (XRD), which confirmed its amorphous-to-semicrystalline nature. Fourier-transform infrared spectroscopy (FTIR) analysis demonstrated the presence of characteristic functional groups without evidence of structural degradation. 
Compatibility studies with selected excipients revealed no significant physicochemical interactions, supporting its suitability for formulation development. Additionally, preliminary stability testing under varying environmental conditions indicated that FP-1 peptide is sensitive to elevated temperature and oxidative stress, necessitating protective formulation strategies such as encapsulation. 
Overall, the findings provide critical insights into the physicochemical attributes of FP-1 peptide and highlight considerations for its successful incorporation into advanced drug delivery systems. These results provide a strong foundation for further formulation development, particularly to enhance stability, bioavailability, and therapeutic efficacy 

Keywords: FP-1 peptide, Preformulation studies, Physicochemical characterization, Stability analysis, Drug–excipient compatibility.

References

[1] Torchilin, V. P. (2005). Recent advances with liposomes as pharmaceutical carriers. Nature Reviews Drug Discovery, *4*(2), 145-160. 
[2] Allen, T. M., & Cullis, P. R. (2013). Liposomal drug delivery systems: From concept to clinical applications. Advanced Drug Delivery Reviews, *65*(1), 36-48. 
[3] Sercombe, L., Veerati, T., Moheimani, F., et al. (2015). Advances and challenges of liposome assisted drug delivery. Frontiers in Pharmacology, *6*, 286. 
[4] Wang, W. (1999). Instability, stabilization, and formulation of liquid protein pharmaceuticals. International Journal of Pharmaceutics, *185*(2), 129-188. 
[5] Manning, M. C., Chou, D. K., Murphy, B. M., et al. (2010). Stability of protein pharmaceuticals: An update. Pharmaceutical Research, *27*(4), 544-575. 
[6] Cleland, J. L., Powell, M. F., & Shire, S. J. (1993). The development of stable protein formulations. Pharmaceutical Research, *10*(3), 310-321. 
[7] Mozafari, M. R. (2005). Liposomes: An overview of manufacturing techniques. Cellular and Molecular Biology Letters, *10*, 711-719. 
[8] Sharma, A., & Sharma, U. S. (1997). Liposomes in drug delivery: Progress and limitations. International Journal of Pharmaceutics, *154*(2), 123-140. 
[9] Danaei, M., Dehghankhold, M., Ataei, S., et al. (2018). Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics, *10*(2), 57. 
[10] Hamley, I. W. (2017). Small bioactive peptides for biomaterials design and therapeutics. Chemical Reviews, *117*(24), 14015-14041. 
[11] Aulton, M. E., & Taylor, K. (2018). Aulton's pharmaceutics: The design and manufacture of medicines. Elsevier. 
[12] Sinko, P. J. (2011). Martin's physical pharmacy and pharmaceutical sciences. Lippincott Williams & Wilkins. 
[13] Lachman, L., Lieberman, H. A., & Kanig, J. L. (1986). The theory and practice of industrial pharmacy. Lea & Febiger. 
[14] Immordino, M. L., Dosio, F., & Cattel, L. (2006). Stealth liposomes: Review of the basic science and clinical applications. International Journal of Nanomedicine, *1*(3), 297-315. 
[15] Kulkarni, S. B., Betageri, G. V., & Singh, M. (1995). Factors affecting microencapsulation of drugs in liposomes. Journal of Microencapsulation, *12*(3), 229-246. 
[16] New, R. R. C. (1990). Liposomes: A practical approach. Oxford University Press. 
[17] Crommelin, D. J. A., & Storm, G. (2003). Liposomes: Quo Vadis? Pharmaceutical Science & Technology Today, *6*(4), 147-153. 
[18] Maherani, B., Arab-Tehrany, E., Mozafari, M. R., et al. (2011). Liposomes: A review of manufacturing techniques and targeting strategies. Current Nanoscience, *7*(3), 436-452. 
[19] Nastruzzi, C. (2000). Liposomes in drug delivery. CRC Press.

[20] Verma, D. D., Verma, S., Blume, G., et al. (2003). Particle size of liposomes influences dermal delivery of substances. International Journal of Pharmaceutics, *258*(1-2), 141-151. 
[21] Mehnert, W., & Mäder, K. (2001). Solid lipid nanoparticles: Production, characterization and applications. Advanced Drug Delivery Reviews, *47*(2-3), 165-196. 
[22] Müller, R. H., Mäder, K., & Gohla, S. (2000). Solid lipid nanoparticles for controlled drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, *50*(1), 161-177. 
[23] Patel, H. M. (1992). Serum opsonins and liposomes: Their interaction and opsonophagocytosis. Critical Reviews in Therapeutic Drug Carrier Systems, *9*(1), 39-90. 
[24] Senior, J. (1987). Fate and behavior of liposomes in vivo. Biochimica et Biophysica Acta, *939*(2), 173-181. 
[25] Gregoriadis, G., & Florence, A. T. (1993). Liposomes in drug delivery: Clinical, diagnostic and ophthalmic potential. Drugs, *45*(1), 15-28. 
[26] Barenholz, Y. (2012). Doxil® — The first FDA-approved nano-drug. Journal of Controlled Release, *160*(2), 117-134. 
[27] Schwendeman, S. P. (2002). Recent advances in the stabilization of proteins encapsulated in injectable PLGA delivery systems. Critical Reviews in Therapeutic Drug Carrier Systems, *19*(1), 73-98.