New Insights Into the Promising Antibacterial Activity of Thiophene or Chromene Moiety Containing Aryl Sulfonamide

Background: Aryl sulfonamides bearing thiophene and chromene moieties have been reviewed for their antibacterial activity and their synthetic methods. Heterocyclic moiety containing aryl sulfonamide compounds are dispersed in nature and are crucial for life. Diverse investigational strategies towards a structural relationship that cognizance upon the exploration of optimized candidates have grown to be extremely crucial. Method: Literature research tells that for a series of thiophene or chromene moiety containing aryl sulfonamide compoundsare vital in medicinal and industrial chemistry.Aryl sulfonamidescontainingheterocyclic moieties display pharmacological activities against pathogenic microbes. Result:Recent various disciplinary reported articles had been cited in this review article to dene the potentialantibacterial properties of thiophene-arylsulfonamide and chromene-arylsulfonamide. Conclusion: The nding of this review conrms the importance of aryl sulfonamidescontaining thiophene or chromene moiety as potential antibacterial agents. These nal resultswill give ideasto the synthesis and developmentof reactions leading to the potential derivativesfor betterpharmacological applications.


Introduction
The millions of people are affected by infectious diseases caused by bacteria which lead to the death of many people worldwide. 1 In developing countries, bacterial infections caused by pathogenic microorganism lead to life-threatening diseases. 2 Presently, antibacterial agents which are commonly in use are Fidaxomicin, Cethromycin, Daptomycin, Torezolid and Solithromycin. 3 Antibacterial agents/Antibiotics are used to kill or control the growth of pathogenic bacteria but the long term usage of antibacterial agents there are chances that bacteria develop resistance against antibacterial/antibiotics. [4][5] In the current situation, multidrug-resistant microbial pathogens have emerged which affect the treatment of infectious diseases. 6 Some of the antibacterial agents like tetracycline are persistent in nature, owing to which they kill bene cial bacteria and cause gastrointestinal distress, yellowing of teeth 7 , increased intestinal peristalsis related to erythromycin therapy 8 ,cause discolouration of skin 9 , condrotoxicity 10 , ototoxicity 11 , retinopathy 12 , lactic acidosis and serotonin syndrome 13 , aplastic anemia 14 , hepatitis 15 , neuromuscular blockade 16 and neoplasia. 17 Numerous pathogenic bacteria occur in nature but the available antibacterial agents or antibiotics have limited inhibitory or killing action on bacteria. Few antibiotics have been found to exhibit activity against Gram-negative and Gram-positive bacteria. [18][19] Organic chemistry has a signi cant impact on our lives, as organic compounds are extensively distributed and play a vital role in various biological elds. This approach has emerged and come to the centre stage in the form of Green Chemistry. The class of sulfonamide is an emerging group of research and most of the organic chemists are engaged in the synthesis of novel sulfonamide. [20][21][22][23] Sulfonamide derivatives are usually prepared by the reaction of ammonia or primary or secondary amines with a sulfonyl chloride. 24 Sulfonamide derivatives have been obtained by the reactivity of sul nic acid salt with highly electrophilic nitrogen from various organic sources. [25][26] Intermolecular free radical reactions of penta uorophenylvinyl sulfonate with subsequent aminolysis reaction are a very convenient route to synthesize sulfonamides. 27 Among the broad variety of medicinal compounds, the functional groups of sulfonamide pharmacophore play a unique role in drug design. 28 Sulfonamidesdisplay a broad range of biological activities,including activity against microbial infection. [29][30] Derivatives of sulfonamides used for the treatments of infectious diseases caused by pathogenic microorganisms due to their growthinhibiting tendency. 31 Compounds carrying sulfonamide core moieties, which construct them signi cantly in drug development, have demonstrated signi cant biological activities. 32 Sulfonamides an antibiotic drug are linked with medicinal activities. Sulfonamides have lately exposed them to be distinctly competent synthons within the practice of diverse treasured biologically active compounds. 33 The derivatives of 9-sulfonylamino scaffold were enhanced antibacterial property against an array of minocycline and tetracycline-resistant pathogens as an example, staphylococcus aureus developed resistant from methicillin, carbapenems, penicillin, quinolone, cephems etc [34][35][36] , while sulfonamides and their combination healing procedures are gaining more attention by means of the day in antimicrobial drug research. 37 As a result, it is viable to expand a sequence of sulfonamides with alkyl amide side chain amendment on carboxyl for enhanced antibacterial e ciency. Sulfonamides have medicinal applications and many of them are broadly utilized in therapeutic as antimicrobial 38 , antitumor [39][40] , anticancer 41 77 developed method for the preparation of alkyl aryl sulfonamide derivatives (10). Aryl hydrazine, hydrazines and potassium metabisul te (K 2 S 2 O 5 ) react together in methylcynide under an air atmosphere at 40 o C. In this process, aryl hydrazine was oxidized by air into aryl radicals and potassium metabisul te was used to generate sulfur dioxide to the formation of sulfonamide derivatives.
Some sulfonamide moieties containing compounds are available for commercial importance and widely used in the clinic. Sulfonamides antibiotics are clinically approved drugs were used to prevent many infectious diseases including pathogenic bacteria known as sulfa drugs Antibacterial drugsul soxazole enhanced antibacterial activities such as p-aminobenzoic acid and sulfamethazine. 92 Sulfamehazineand tiamulin mixture possessed synergistic antibacterial properties against pathogenic bacteria were isolated from pigs. 93 The chlorothiazide and hydro chlorothiazide are the class of sulphones series were evaluated as antibacterial and antifungal. 94 Sulfonamide core moiety scaffolds have been found to exhibit diverse signi cant biological properties also found in some natural compounds. Generally, sulfonamide moiety compounds were isolated from marine actinomycetes. Cytotoxic monoterpene-alkaloid (-)-altemicidin were isolated from active fractions of Streptomyces sioyaensis. 95 (-)-Altemicidin showed inhibitory activity against bacterial strains (Muralidharan andDeecaraman, 2017) 96 were reported mild growth inhibition against Xanthomonas species. The bromotyrosine-cysteine derivatives, psammaplin A and C were extracted from the sponge Psammaplysilla purpurea are e cient antibacterial agents. 97 Nucleocidin are uorinated sugar structure used as an antibiotic and it were obtained from soil microbe Streptomyces calvus 98 andStreptomyces albo avus. 99 In addition, potent antibacterial activity against both Gram (positive and negative) pathogenic bacteria strains.

Thiophene moiety containing sulfonamide derivatives
For the preparation of thiophene moiety containing sulfonamide derivatives via Suzuki cross-coupling reaction, a convenient approach was published in the literature. 100 Thiophene moiety containing compounds are excellent bioactive agents. They have been found to exhibit various biological activities such as antimicrobial [101][102] , anti-HIV 103 , anti-in ammatory 104 , anticancer. 105 Cytochrome inhibition has been observed in some thiophene derivatives. 106 Thiophene-2-sulfonamides derivatives are also regarded as inhibitors of carbonic anhydrase, and the literature indicates that diuretic activity is also seen in many of its simple derivatives. The reaction of benzenesulfonamide and (benzothiophen-3-yl)-3-chloropropan-1-one using THF as solvent and K 2 CO 3 as catalyst affords substituted benzothiophene (N-aryl) sulfonamide (4) in good yield. 111 The synthesized thiophene aryl sulfonamide (5) was evaluated in-vitro antibacterial activity against pathogenic bacteria such as B.subtilis, E.coli, B. megaterium and P. ourescens. 112 Thiophene moiety containing N-substituted aryl sulfonamides (6) have been synthesized from the reaction of 3-(thiophene-2-ylmethylamino)propanenitrile with p-toluenesulfonyl chloride using Et 3 N as catalyst and DCM as a solvent. 113  Thiophene-sulfonamide compound does not exist in a natural source. Thiophene exists in natural sources with promising biological applications but the compounds of thiophene moiety sulfonamide scaffold only available in synthesized form.

Chromene moiety containing sulfonamide derivatives
The core entity of several biologically vigorous natural products, as well as synthetic therapeutic agents, consists of unsaturated 1-benzopyran derivatives, widely known as chromenes. 122 The chromene nucleus is, thus, widely known in medicinal chemistry as a privileged scaffold. 123 4H-chromene and 2H-chromene are an isomeric form of each other, which depending on their substitution pattern, can be differentiated by the site of unsaturation and show a range of pharmacological properties. Chromene moieties play a signi cant role with structural aryl sulfonamide scaffold which can be easily transformed into functionalized diverse biologically active molecules. 124 Naturally occurring 125 and synthetic chromene compounds possess antibacterial properties. 126 A number of pathways are available for their synthesis, but there is a signi cant need for approaches that include chromenes from precursors that are readily available. 127 Some synthesized sulfonamide derived chromenes were investigated for antibacterial, antifungal and cytotoxic. 128 Chromone is known as a single molecule that can be paired with various receptors groups. 129 Due to its useful activities and low toxicity, chromone is regarded as a desirable source for the synthesis of new drugs. Chromene-sulfonamide compound does not exist in a natural source. Chromene and its derivatives exist in various natural sources with promising biological applications but the compounds of chromene moiety sulfonamide scaffold only available in synthesized form.

Conclusion
Aryl sulfonamides bearing thiophene or chromene moieties have been reviewed for their antibacterial activity and their synthetic methods.The review will provide insight to readers,to tap the potential of these classes of compounds. More compounds of these classes need to be synthesized with wide structural variation in order to establish structure-activity relationship and nd out new compounds having promising antibacterial properties.

Declarations Con ict of Interest
There is no con ict of interest between coauthor.

Funding
No funding was supported by any organizations for this work.

Figure 2
Advance method for the preparation of aryl sulfonamides.  Natural bioactive sulfonamide compounds Figure 5 Preparation methods of thiophene-aryl sulfonamides Figure 6 Preparation methods of myriad thiophene containing aryl sulfonamides Bioactivethiophene-sulfonamides agents Figure 9 Preparation methods of chromene containing aryl sulfonamides Figure 10 Preparation methods of myriad chromene containing aryl sulfonamides

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