Abstract
Coumarin sulfonamide is a heterocyclic pharmacophore and an important structural motif which is a core and integral part of different therapeutic scaffolds and analogues. Coumarin sulfonamides are privileged and pivotal templates which have a broad spectrum of applications in the fields of medicine, pharmacology and pharmaceutics. Coumarin sulfonamide exhibited versatile and myriad biomedical activities such as anti-bacterial, antiviral, antifungal, anti-inflammatory and anti-cancer. This review article focuses on the structural features of coumarin sulfonamide derivatives in the treatment of different lethal diseases on the basis of structure-activity relationships (SAR). The plethora of research cited in this review article summarizes and discusses the various substitutions around the coumarin sulfonamide nucleus which have provided a wide spectrum of biological activities and therapeutic potential that has proved attractive to many researchers looking to exploit the coumarin sulfonamide skeleton for drug discovery and the development of novel therapeutic agents.
Introduction
Coumarins (1) are natural lactones [1] and belong to a class of fused six-membered oxygen-containing benzoheterocycles [2, 3, 4] in which the benzene ring (2) is fused with α-pyrone (3) [5] (Figure 1). Sulfonamides (4) (Figure 1) contain the pharmacologically active group – SO2NH- which is part of many clinical drugs [6]. Coumarins received great interest in the literature from synthetic scientists, medicinal chemists and pharmacists because of their exciting, versatile and broad-spectrum biological activities. Coumarin and its derivatives have proven to be significant precursors for synthesizing a wide variety of medicinal agents [7].
Structure of coumarin (1), benzene (2), α-pyrone (3) and sulfonamide (4).
Coumarin is the basis of a diverse library of chemical structures with promising biological profiles, interesting biological activities and therapeutic functions, which include vasorelaxant, immunosuppressant (5) [8], anti-psoriasis, anti-inflammatory (6) [9, 10], vasodilator (7) [11], anticoagulant (8) [12], anti-bacterial (9) [8], antifungal (10) [13, 14, 15, 16], anti-allergic, antidepressant [17], antioxidant [18], anti-cancer [19, 20, 21, 22, 23], anti-HIV (11) [24], anti-diabetic [25, 26], antiviral, anti-proliferative [27], antithrombotic [8] and antimicrobial [28, 29]. Some coumarin based marketed drugs are shown in Figure 2.
Structures of different coumarin based drugs 5-11.
The sulfonamide moiety itself exhibits pharmacological activities such as anti-bacterial (12) [30], anti-inflammatory (13) [31], anti-tumor (14) [32, 33, 34, 35, 36, 37, 38, 39], anti-carbonic anhydrase (15) [40], anti-HIV (16), antimicrobial (17), anti-neoplastic [41], anti-convulsant and anti-cancer [42]. Some sulfonamide based marketed drugs are shown in Figure 3.
Structures of different sulfonamide based marketed drugs 12-17.
Different coumarin sulfonamide hybrid structures such as CAI17 (18) demonstrated anti-metastatic activity. Sulfocoumarin (19) and chlorophenyl substituted coumarin sulfonamide scaffolds (20) showed remarkable selectivity against human carbonic anhydrase IX and XII [43, 44] (Figure 4).
Structures of biologically active coumarin sulfonamide scaffolds 18-20.
This article summarizes the recent literature on the advances in the therapeutic potential of bio-active coumarin sulfonamide hybrid structures which displayed excellent anti-cancer, anti-bacterial, antiviral, antifungal and anti-inflammatory activities.
Literature Review on Pharmacological Profile of Coumarin Sulfonamide Scaffolds
The Coumarin sulfonamide moiety can be termed as a ‘Master Key’ as it is an important and privileged structural motif which is an integral part of diversified hybrid structural libraries of compounds targeted to elicit varied pharmacological activities. The pharmacological profile of coumarin sulfonamide can be categorized into the following classes:
Anti-cancer activities
Anti-oxidant activities
Alkaline phosphatase inhibitory effects
Anti-inflammatory activities
Anti-bacterial activities
Antifungal activities
Anti-cancer Activities of Coumarin Sulfonamide Derivatives
Cancer is a complex and sometimes fatal disease which poses a great challenge to the medical R&D (research and development) scientific community, who must develop drugs, medicinal therapeutic agents and procedures for safer treatment [45]. Coumarin sulfonamide-based scaffolds and hybrid structures possess promising therapeutic potential against various cancer cell lines and carbonic anhydrases (CA). CAs are metalloenzymes and are also known as carbonate dehydratases, which are divided into different forms, including secreted CA isozymes, five membrane bound isozymes, two mitochondrial forms and five cytosolic forms [46]. Isozymes exhibited diverse and wide spectrum inhibition profiles, with specific isoenzymes displaying various biological responses [47, 48]. CAI inhibitory potential ranges from diuretics, antiglaucoma agents, anti-obesity and anti-epileptic drugs, to anticancer agents. The two main classes of CAIs are metal-complexing anions and unsubstituted sulfonamides and their bioisosteres. The action mechanism of CAIs is either to bind to the Zn2+ ion of the enzyme to generate a tetrahedral adduct with a non-protein zinc ligand or to make a trigonal bipyramidal species by addition to the metal coordination sphere [49, 50, 51]. Anti-cancer CAI activities of coumarin sulfonamide scaffolds are discussed in more detail below.
Wang, et al. [52] reported the synthesis of substituted coumarin sulfonamide derivatives. These synthesized scaffolds were screened against B16-F10 (mouse melanoma) and MCF-7 (breast carcinoma) cell lines. The substituted pyrimidine based coumarin benzene sulfonamide analogue (21) was the best inhibitor against carbonic anhydrases, such as cytosolic off-target isoform (hCAs-II), with an IC50 value of 0.063 μM as compared to the reference drug AZA (Acetazolamide) which had an IC50 value of 0.016 μM and SA (sulfanilamide) with an IC50 value of 0.26 μM. Scaffold (21) showed the best anti-cancer activity against the trans membrane tumor-associated isoform (hCAs-IX) with an IC50 value of 0.024 μM when compared with AZA and SA (IC50 values of 0.028 and 0.29 μM respectively). Wagner, et al. [53] endeavored to synthesize coumarinyl sulfonamide derivatives, which were tested against various carbonic anhydrase inhibitor isoforms, such as hCA-I (cytosolic), hCA-II, hCA-IX and hCA-XII (trans membrane, tumor-associated isozymes). The amino based coumarin disulfonamide scaffold (22) was the most potent inhibitor of the synthesized derivatives and exhibited good inhibition against the hCA-IX inhibitor with a Ki value of 14 nM as compared to AZA which had a Ki value of 25 nM. Scaffold (22) showed good inhibition activity against the hCA-XII inhibitor with a Ki value of 6 nM compared to AZA which had a Ki value of 2.5 nM.
Pyrimidine and coumarinyl sulfonamide scaffolds 21 and 22 which displayed anti-cancer activity.
Thiazole based coumarin analogue 23 which displayed anti-cancer activity.
Kurt, et al. [54] synthesized substituted benzene sulfonamide based coumarylthiazole hybrid structures and demonstrated their anti-cancer activity for different human carbonic anhydrase isoforms such as hCA I and hCA II. Among these compounds, the thiazole based coumarin naphthalene sulfonamide scaffold (23) showed the strongest inhibition against hCA I with an IC50 value of 5.63 μM. Derivative (23) also demonstrated remarkable inhibition against hCA II with an IC50 value of 8.48 μM.
Chandak, et al. [55] evaluated twenty four sulfonamide bearing coumarin scaffolds showing inhibition against different selected isoforms of human carbonic anhydrase (hCA I, II, IX and XII). Among all of those screened, the amino thiazole based coumarin benzene sulfonamide compound (24) showed potent inhibitory activity against hCA IX with a Ki value of 25.04 nM as compared to the reference compound AZA which had a Ki value of 25 nM. Scaffold (24) showed potent inhibitory activity against hCA XII when compared with AZA, with Ki values of 3.94 and 5.7 nM respectively. Zaib, et al. [56] synthesized amino benzene sulfonamide-thiourea derivatives which were studied for their inhibitory activity on carbonic anhydrase. The substituted amino sulfonylphenyl based coumarin thiourea (25) proved to be the most potent inhibitor against hCA II (cytosolic enzymes) with an IC50 value of 0.052 ± 0.01 μM as compared to AZA (IC50 value 0.96 ± 0.18 μM). Scaffold (25) showed the best inhibition due to the substitution of 3-aminosulfonylphenyl on the ortho position of the thiourea ring.
The literature cited in this article indicates that inhibition of tumor-associated CA isozymes may be useful in the treatment of cancer. The coumarin sulfonamides demonstrated a key role in the cure and management of various types of cancers tumors, acting as anti-proliferative and therapeutic agents as discussed below.
Amin, et al. [57] synthesized coumarin-pyrazoline analogs containing a phenylsulfonyl moiety and screened for their anti-cancer activities against different tumor cell lines. The chloro-phenylsulfonyl substituted pyrazol based methoxy coumarin scaffold (26) exhibited excellent anti-cancer activity against MCF7 (breast cancer cell line) and HCT-116 (colon cancer cell line). Scaffold (26) showed activity against the HCT-116 cell line with an IC50 value of 0.01 μM, compared with the reference compound doxorubicin which had an IC50 value of 0.63 μM. Aoki, et al. [58] introduced a sulfonamide moiety containing coumarin derivatives and screened for its inhibitory activity. Scaffold (27) exhibited potent inhibition with an IC50 value of 8 nM against HCT-116 cell growth. Scaffold (27) further demonstrated a high antitumor activity in vivo against the HCT 116 xenograft with an ED50 of 4.8 mg/kg.
Pingaew, et al. [59] prepared 1, 2, 3-triazole based coumarin sulfonamide derivatives and screened for their aromatase anti-cancer activity against various cell lines. The dimethoxy substituted dihydroisoquinolin based coumarin triazole scaffold (28) demonstrated aromatase anti-cancer activities against Met374 and Ser478 with an IC50 value of 0.2 ± 0.1 μM as compared with standard compounds Ketoconazole and letrozole which had IC50 values of 2.6 ± 0.7 μM and 0.0033 ± 0.0004 μM, respectively. Sawy, et al. [60] reported on the effect of a series of sulfonyl coumarin derivatives against the HepG2 (hepatocellular carcinoma) cell line. The substituted amino sulfonyl based coumarin pyrazol (29), an anti-angiogenic agent, possessed an MMP dependent anti-migration activity against HepG2.
Coumarin sulfonamide derivatives 24 and 25 which displayed anti-carbonic anhydrase activity.
Coumarin sulfonamide derivatives 26 and 27 which displayed anti-colon and breast cancer activities.
Sabt, et al. [61] synthesized coumarin substituted sulfonamide derivatives and studied their anti-proliferative activity against HepG2 (hepatocellular carcinoma), MCF-7 (breast cancer) and Caco-2 (colon cancer) cell lines. The phenyl thiazole based coumarin sulfonamide scaffold (30) exhibited remarkably high activity against HepG2 cells with an IC50 value of 3.48 ± 0.28 μM when compared to the reference drug Doxorubicin which had an IC50 value of 5.43 ± 0.24 μM. Debbabi, et al. [62] synthesized cyano-acetohydrazonoethyl-N-ethyl-N-methyl benzene sulfonamide analogues and determined their in-vitro anti-cancer and antimicrobial activities. Among all synthesized compounds, the hydrazono based coumarin benzene sulfonamide scaffold (31) showed the best activity against MCF-7 with an IC50 value of 1.08 μg/mL when compared with the reference drug MTX (methotrexate) which had an IC50 value of 12.3 μg/mL.
Holiyachi, et al. [63] synthesized a diverse library of coumarin-benzimidazole hybrid structures and evaluated their anti-cancer activities. Among these derivatives, the tosyl-benzimidazole substituted methyl coumarin scaffold (32) exhibited excellent anti-cancer activity against HeLa (human cervix cancer cell line) in comparison with the reference compound Adriamycin (ADR). The tosyl-benzimidazole substituted methoxy coumarin scaffold (33) also displayed anti-cancer activity against HeLa when compared to ADR. The tosyl-benzimidazole substituted based bromo coumarin imidazole (34) exhibited remarkably high activity against HT 29 when compared to ADR. The SAR studies indicated that the diversified anti-cancer activity against different cell lines displayed by the synthesized compounds (32), (33) and (34) was due to the electronic effects of the CH3, OCH3 and Br substituents attached to the coumarin rings.
Anti-oxidant activities of coumarin sulfonamides derivatives
Kurt, et al. [64] synthesized sulfonamide-substituted coumarylthiazole derivatives and evaluated their antioxidant activities using the radical scavenging 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assay and cupric reducing antioxidant capacity (CUPRAC) assay. The methoxy substituted thiazole based benzene sulfonamide scaffold (35) demonstrated ABTS anti-oxidant activity with an IC50 value of 48.83 ± 1.38 μM as compared to the standard reference drug quercetin which had an IC50 value of 15.49 ± 2.33 μM. Scaffold (35) showed excellent antioxidant cupric reduction capabilities with an A0.50 value of 23.29 ± 0.02 μM while the reference quercetin had an A0.50 value of 18.47±0.04 μM. Saeedi, et al. [65] synthesized sulfonamide and amide derivatives containing coumarin moieties and screened for their antioxidant activities. The antioxidant activity of the sulfamoylphenyl acetamide based 4-methyl coumarin derivative (36) was determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging method and ferric reducing antioxidant power (FRAP) assay. The hybrid structure (36) demonstrated the best DPPH activity with an IC50 value of 0.66 ± 0.01 mM as compared to quercetin which had an IC50 value of 8.12 ± 0.13 mM. Scaffold (36) exhibited the best antioxidant potential using DPPH as opposed to FRAP. The SAR studies revealed that derivative (36) showed good antioxidant potential due to substitution of a methyl group on position 4 of the coumarin ring.
Coumarin sulfonamide derivatives 28 and 29 which displayed anti-cancer therapeutic potential.
Substituted coumarin sulfonamide derivatives 30 and 31 which displayed anti-proliferative and anti-cancer activities.
Alkaline phosphatase inhibitory effects of coumarin sulfonamide derivatives
Iqbal, et al. [66] synthesized tricyclic-fused coumarin sulfonates and studied their excellent inhibitory activities against alkaline phosphatase isozymes such as h-TNAP (tissue alkaline phosphatase) and h-IAP (intestinal alkaline phosphatase). Among these derivatives, the substituted methyl based coumarin benzene sulfonate derivative (37) was the most active inhibitor against h-TNAP with an IC50 value of 0.38 ± 0.01 μM as compared to the reference drug levamisole which had an IC50 value of 20.2 ± 1.90 μM. The 4-fluoro based coumarin benzene sulfonate derivative (38) was the strongest inhibitor against h-IAP with an IC50 value of 0.45 ± 0.02 μM in comparison with the reference compound L-phenylalanine which had an IC50 value of 100 ± 3.15 μM.
Methyl, methoxy and bromo substituted coumarin sulfonamide derivatives 32, 33 and 34 which displayed anti-cancer activities.
Coumarin sulfonamide derivatives 35 and 36 which displayed antioxidant activities.
Coumarin sulfonamide derivatives 37 and 38 which displayed alkaline phosphatase inhibitory activities.
Coumarin sulfonamide derivatives 39 and 40 which displayed anti-cancer activities.
Coumarin sulfonamide derivative 41 which displayed anti-inflammatory activity.
Pyrazole based coumarin sulfonamide 42 scaffold – a COX-2 and 5-LOX inhibitor.
Pyraole based coumarin sulfonamide – a COX-1 and COX-2 inhibitor scaffold 43.
Salar, et al. [67] reported a synthetic methodology to obtain coumarin derived sulfonate derivatives and investigated their inhibitory properties against h-TNAP and h-IAP. The substituted cyano based coumarin methoxy benzenesulfonate (39) was the best inhibitor against h-TNAP with an IC50 value of 0.58 ± 0.17 μM as compared to reference compound L-Phenylalanine which had an IC50 value of 100.1 ± 3.15 μM. The SAR studies demonstrated that analogue (39) exhibited the best inhibition activity due to the substitution of a cyano (CN) group at position 3 and a methoxy (OMe) group at position 4 of the coumarin ring. The cyano based coumarin nitro benzenesulfonate scaffold (40) was the best inhibitor against h-IAP with an IC50 value of 1.11 ± 0.15 μM when compared with the reference compound levamisole which had an IC50 value of 20.21 ± 1.9 μM. The SAR studies indicated that the hybrid structure (40) showed the best inhibition due to the substitution of an NO2 group at position 4 of the phenyl ring.
Coumarin sulfonamide scaffolds 44 and 45 which displayed anti-bacterial activities.
Anti-inflammatory activities of coumarin sulfonamide derivatives
N. Chandak, et al. [68] synthesized a novel and biologically active series of eighteen coumarinyl thiazole carrying benzene sulfonamide derivatives. These scaffolds were investigated for their in vitro antimicrobial activity and in vivo anti-inflammatory activity. The chlorophenyl substituted pyrazol based coumarin benzene sulfonamide scaffold (41) had the most powerful anti-inflammatory activity against cyclooxygenase (COX-1 and COX-2) when compared to the standard drug indomethacin.
Shen, et al. [69] reported on synthetic strategies to afford pyrazole moiety containing coumarin sulfonamide structures and evaluated their anti-proliferation activity in vitro. Scaffold (42) was highly biologically active against COX-2 with an IC50 value of 0.23 ± 0.16 μM when compared to the reference drug celecoxib which had an IC50 value of 0.41 ± 0.28 μM. Scaffold (42) exhibited inhibitory activity against 5-LOX with an IC50 value of 0.87 ± 0.07 μM, in comparison with the reference standard zileuton which had an IC50 value of 1.35 ± 0.24 μM. Derivative (42) demonstrated the most potent activity (4.48 ± 0.57 μM) against A549 (human lung cell line) as compared to celecoxib which had an IC50 value of 7.68 ± 0.55 μM.
Yuan, et al. [70] synthesized coumarin sulfonamide derivatives and screened for their cyclooxygenase (COX-2) inhibitory and anti-cancer activities. The chloro-coumarin substituted benzene sulfonamide scaffold (43) exhibited the most powerful anti-proliferative and inhibitory activity against COX-2 with an IC50 value of 0.09 μM compared with the reference compound celecoxib which had an IC50 value of 0.31 μM. Scaffold (43) demonstrated remarkable antiproliferative and inhibitory activity against COX-1 with an IC50 value of 48.20 μM as compared to celecoxib which had an IC50 value of 43.37 μM. The hybrid structure (43) also showed excellent antiproliferative and inhibitory activity against HeLa cells (cervix cancer cell) with an IC50 value of 0.36 μM when compared to celecoxib which had an IC50 value of 7.79 μM.
Anti-bacterial activities of coumarin sulfonamide derivatives
Mostajeran, et al. [1] reported the synthesis of coumarin-6-sulfonamide compounds and tested their anti-bacterial potential in vitro against ATCC35218 (Escherichia coli) and ATCC6538 (Staphylococcus aureus). The thiazole based coumarin sulfonamide scaffold (44) demonstrated remarkably high anti-bacterial activity against S. aureus (ATCC6538) with a zone of inhibition (ZI) value of 24 mm as compared to the reference drugs ampicillin and chloramphenicol which had ZI values of 28 mm and 19 mm, respectively. Scaffold (44) also exhibited strong anti-bacterial activity against E. coli (ATCC35218) with a ZI value of 16 mm as compared to ampicillin and chloramphenicol which had ZI values of 15 and 22 mm, respectively.
Chohan, et al. [71] introduced a series of 4-hydroxy-coumarin sulfonamides derivatives and studied their invitro anti-bacterial activities for different gram-positive (S. aureus, B. subtilis) and gram-negative (S. flexneri, S. typhi, E. coli, P. aeruginosa) bacteria. The amino substituted ethyl coumarin benzene sulfonamide scaffold (45) showed the best activity against E. coli with a ZI value of 10 mm as compared to the standard reference drug imipenem which had a ZI value of 30 mm. Scaffold (45) also showed the best activity against S. flexenari with a ZI value of 09 mm when compared to imipenem which had a ZI value of 27 mm.
Basanagouda, et al. [72] synthesized a number of sulfonamide containing 4-azidomethyl coumarin derivatives with antimicrobial activity. The series of newly reported compounds exhibited in vitro anti-bacterial activity against different bacteria strains, such as Streptococcus faecalis (MTCC 3382), Staphylococcus aureus (MTCC 3160), Bacillus subtilis (MTCC 297), Pseudo-monas aeruginosa (MTCC1034), Klebsiella pneumonia (MTCC 3384) and Escherichia coli (MTCC1089). The azidomethyl substituted coumarin based amide scaffold (46) showed anti-bacterial activity against S. faecalis with an MIC value of 1 μg/mL in comparison to the reference drug ciprofloxacin which had an MIC value of 1 μg/mL. Scaffold (46) showed anti-bacterial activity against P. aeruginosa with an MIC value of 31.25 μg/mL as compared to ciprofloxacin which had an MIC value of 1.0 μg/mL. Scaffold (46) also showed anti-bacterial activity against K. pneumonia with an MIC value of 1.0 μg/mL when compared with ciprofloxacin which had an MIC value of 1.0 μg/mL. The substituted azidomethyl coumarin based amide showed anti-bacterial activity against S. faecalis with an MIC value 1.0 μg/mL when compared with ciprofloxacin which had an MIC value of 1.0 μg/mL. Scaffold (47) showed the highest anti-bacterial activity against P. aeruginosa with an MIC value of 1.0 μg/mL in comparison with ciprofloxacin which had an MIC value of 1 μg/mL. Scaffold (47) also showed anti-bacterial activity against K. pneumonia with an MIC value 1 μg/mL when compared with ciprofloxacin which had an MIC value of 1 μg/mL.
Halogens substituted coumarin sulfonamide analogues 46 and 47 which displayed anti-bacterial potential.
Antifungal coumarin sulfonamide derivatives 48, 49 and 50.
Antifungal activities of coumarin sulfonamide derivatives
Chohan, et al. [71] evaluated 4-hydroxycoumarin sulfonamides hybrids for their antifungal activity in-vitro against A. flavus, T. longifusus, C. glaberata, M. canis, F. solani and C. albicans fungal strains. The amino substituted coumarin benzene sulfonamide scaffold (48) showed significant activity against M. canis with an MIC value of 74 μg/mL in comparison to the reference drug miconazole (MIC = 98.4 μg/mL). The amino substituted pyrimidinyl based coumarin sulfonamide derivative (49) exhibited significant activity against M. canis with an MIC value of 86 μg/ mL in comparison with miconazole (MIC = 98.4 μg/mL). The substituted amino isoxazolyl coumarin benzene sulfonamide (50) showed remarkably high activity against F. solani with a MIC value of 69 μg/mL as compared to miconazole (MIC = 73.25 μg/mL). Compound (49) also demonstrated excellent anti-fungal activity against F. solani with a MIC value of 82 μg/mL which was greater than the reference standard drug miconazole which had a MIC value of 73.25 μg/mL.
Basanagouda, et al. [72] reported the synthesis of 4-azidomethyl substituted coumarin sulfonamide derivatives. All the prepared coumarin sulfonamide derivatives were screened for their antifungal activity in vitro against various fungal strains such as Mucor fuscus, Candida albicans, Fusarium oxysporum, Aspergillus fumigatus, Penicillium chrysogenum and Aspergillus niger. The substituted azidomethyl coumarin sulfonic acid scaffold (51) showed excellent anti-fungal activity against C. albicans with a MIC value of 1 μg/mL in comparison with the reference drug fluconazole (MIC = 8 μg/mL). The substituted azidomethyl based coumarin sulfonic acid (52) exhibited the best anti-fungal activity against C. albicans with a MIC value of 4 μg/mL while fluconazole had a MIC value of 8 μg/mL. The azidomethyl based coumarin sulfonic acid derivative (53) demonstrated activity against C. albicans with a MIC value of 4 μg/mL in comparison to fluconazole which had an MIC value of = 8 μg/mL.
Conclusion
The literature discussed in this article revealed that coumarin sulfonamide scaffolds and analogues displayed versatile biological activities, due to which these derivatives have high potential for the development of new entities for the treatment of different diseases. The coumarin sulfonamide derivatives showed promising profiles of enzyme inhibitory and anti-cancer activities. The coumarin sulfonamide scaffolds exhibited a broad spectrum of biological activities in the fields of medicine, pharmaceutics and pharmacology . The literature cited in this review article indicated that some coumarin sulfonamide derivatives have higher potency and better therapeutic indexes than the reference drugs. Coumarin sulfonamide derivatives demonstrated excellent and promising activities on the basis of SAR against different types of bacterial strains, fungal strains and against a variety of cancer cell lines. The biological profile of coumarin sulfonamide derivatives represents a fruitful matrix for future drug discovery as well as the design and development of better medicinal agents for the safer treatment of various diseases.
Antifungal coumarin sulfonamide derivatives 51, 52 and 53.
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