The dapsone/flavone cocrystal system served as a benchmark for both experimental and virtual screening methods. Expanding beyond this, two additional active pharmaceutical ingredients (APIs), sulfanilamide and sulfaguanidine, structurally related to dapsone were chosen to investigate the impact of substituents on cocrystal formation. The experimental screening involved mechanochemical methods, slurry experiments, hot-melt extrusion, and the contact preparation method. The virtual screening focused on crystal structure prediction (CSP), molecular complementarity, hydrogen-bond propensity, and molecular electrostatic potentials. The CSP studies not only indicated that each of the three APIs should form cocrystals with flavone but also reproduced the known single- and multicomponent phases. Experimentally, dapsone/flavone cocrystals A_CC, B_CC, C_CC, and D_CC were reproduced, C_CC was identified as a nonstoichiometric hydrate, and a fifth cocrystal (E_CC), a t-butanol solvate, was discovered. The cocrystal polymorphs A_CC and B_CC are enantiotripically related, and D_CC, exhibiting a different stoichiometric ratio, is enthalpically stabilized over the other cocrystals. For the sulfaguanidine/flavone system, two novel, enantiotripically related cocrystals were identified. The crystal structures of two cocrystals and a flavone polymorph were solved from powder X-ray diffraction data, and the stability of all cocrystals was assessed through differential scanning calorimetry and lattice energy calculations. Despite computational indications, a diverse array of cocrystallization techniques did not result in a sulfanilamide/flavone cocrystal. The driving force behind dapsone's tendency to cocrystallize with flavone can be attributed to the overall strength of flavone interactions in the cocrystals. For sulfaguanidine, the potential to form strong API···API and API···coformer interactions in the cocrystal is a contributing factor. Furthermore, flavone was found to be trimorphic.

07 Feb 2024·Crystal Growth & Design

Comprehensive Insights into Sulfaguanidine in the Solid State: An Experimental and Computational Study

Article

Author: Braun, Doris E ; Widauer, Alexandre ; Petrick, Tom L

A thorough re-examination of sulfaguanidine's (SGD) solid-state behavior was conducted, 65 years after the initial report on SGD polymorphism. This investigation focuses on the polymorphic nature of the compound, the formation of hydrates and solvates, and the pivotal role of experimental and computational methods in screening, assessing stability, and understanding transformation processes. The findings confirm the presence of five anhydrates (AH-I-V), two monohydrate polymorphs (Hy1-I and Hy1-II), and nine solvates (with tetrahydrofuran, methanol, ethanol, t-butanol, acetone, cyclohexanone, dimethyl sulfoxide, dimethyl formamide, and dimethyl acetamide). Notably, nine novel structures-two anhydrates and seven solvates-are reported, solved from powder X-ray diffraction data. Calorimetric measurements have revealed that AH-II is the thermodynamically stable polymorph at room and low temperatures. In contrast, AH-I emerges as the stable polymorph at higher temperatures, yet it exhibits remarkable kinetic stability at RT and demonstrates greater stability in terms of hydration. The anhydrate forms exhibit distinctive packing arrangements, while the two hydrates share a close structural resemblance. Among the seven structurally characterized solvates, only the tetrahydrofuran and dimethyl sulfoxide solvates are isostructural. Controlled desolvation experiments enabled the formation of AH-I, AH-II, and, notably, AH-V for the first time. The anhydrate and monohydrate crystal structure prediction studies reveal that the computed lowest-energy structures correspond to experimentally observed forms and propose models for the elusive AH-IV structure. Overall, the exploration of SGD's solid-state landscape confirms a rich array of highly stable H-bonding motifs and packing arrangements, positioning this study as an ideal model for complex solid-state systems and shedding light on its intricate solid-state nature.

05 Dec 2023·ACS Omega

Exploring the Potential of New Benzamide-Acetamide Pharmacophore Containing Sulfonamide as Urease Inhibitors: Structure–Activity Relationship, Kinetics Mechanism, and In Silico Studies

Article

Author: Ahmad, Muhammad ; Zargar, Seema ; Ahmad, Saghir ; Wani, Tanveer A ; Ahmed, Mahmood ; Ali, Ijaz ; Imran, Muhammad ; Muddassar, Muhammad ; Yousaf, Numan ; Abdul Qadir, Muhammad

The search for novel drug scaffolds that can improve effectiveness and safety through drug conjugates is a promising approach. Consequently, drug conjugates constitute a dynamic field of study and advancement within medicinal chemistry. This research demonstrates the conjugation of diclofenac and mefenamic acid with sulfa drugs and their screening for urease inhibition. These conjugates' structural confirmation was performed using elemental analysis and spectroscopic methods, including IR, ¹H NMR, and ¹³C NMR. Diclofenac conjugated with sulfanilamide (4), sulfacetamide (10), and mefenamic acid conjugated with sulfanilamide (12), and sulfamethoxazole (17) was found potent and demonstrated urease inhibition competitively, with IC₅₀ (μM) values 3.59 ± 0.07, 5.49 ± 0.34, 7.92 ± 0.27, and 8.35 ± 0.26, respectively. Diclofenac conjugated with sulfathiazole (6), sulfamerazine (8), and sulfaguanidine (11), while mefenamic acid conjugated with sulfisoxazole (13), sulfathiazole (14), and sulfadiazine (15) exhibited a mixed mode of urease inhibition. The IC₅₀ (μM) values were 16.19 ± 0.21, 9.50 ± 0.28, 4.35 ± 0.23, 15.86 ± 0.25, 14.80 ± 0.27, and 7.92 ± 0.27, respectively. Furthermore, molecular docking studies were employed to predict the binding pose of competitive inhibitors at the urease active site. These conjugates generated stable complexes with the urease protein observed through molecular dynamics (MD) simulations, where no conformational changes occurred throughout the simulations. These results highlight the potential for approved therapeutic molecule conjugates to give rise to new categories of pharmacological agents for urease inhibition. The structural similarity of sulfonamides with urea allows them to compete with urea for binding to the active site of the urease enzyme. Sulfonamides and nonsteroidal anti-inflammatory drugs (NSAIDs) can interact hydrophobically with the active site of the urease enzyme, which may disturb its structure and catalytic activity. Therefore, these conjugates may be helpful in the development of novel pharmacological agents for the treatment of a variety of illnesses in which the urease enzyme is involved.

100 Deals associated with Sulfaguanidine

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KEGG	Wiki	ATC	Drug Bank
D02437	Sulfaguanidine	A07AB03	DB13726

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