Pharmaceutical and medicinal significance of sulfur (SVI)-Containing motifs for drug discovery: A critical review

Abstract

Sulfur (S^VI) based moieties, especially, the sulfonyl or sulfonamide based analogues have showed a variety of pharmacological properties, and its derivatives propose a high degree of structural diversity that has established useful for the finding of new therapeutic agents. The developments of new less toxic, low cost and highly active sulfonamides containing analogues are hot research topics in medicinal chemistry. Currently, more than 150 FDA approved Sulfur (S^VI)-based drugs are available in the market, and they are widely used to treat various types of diseases with therapeutic power. This comprehensive review highlights the recent developments of sulfonyl or sulfonamides based compounds in huge range of therapeutic applications such as antimicrobial, anti-inflammatory, antiviral, anticonvulsant, antitubercular, antidiabetic, antileishmanial, carbonic anhydrase, antimalarial, anticancer and other medicinal agents. We believe that, this review article is useful to inspire new ideas for structural design and developments of less toxic and powerful Sulfur (S^VI) based drugs against the numerous death-causing diseases.

Keywords: Biological activities; Docking; SAR; Sulfonamides; Sulfonyl (S(VI)).

Graphical abstract

Fig. 1

Some of the sulfonyl or sulfonamides containing heterocycles as potential antimicrobial agents.

Fig. 2

Some antimicrobial activities of potent sulfonyl or sulfonamides hybrids.

Fig. 3

Sulfonyl of sulfonamides with antimicrobial properties.

Fig. 4

Sulfonyl of sulfonamides as antimicrobial agents.

Fig. 4

Sulfonyl of sulfonamides as antimicrobial agents.

Fig. 5

Some representative sulfonyl of sulfonamides as potent anti-diabetic agents.

Fig. 6

Sulfonyl of sulfonamides as antidiabetic agents.

Fig. 7

Docked pose of compound 139 (turquoise colour) showing hydrogen bond interactions (red dashed lines) with amino acids in the binding site of PPARγ. The ligand and amino acids are represented as stick and thin tube model. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 8

Sulfonyl of sulfonamides as anti-diabetic agents.

Fig. 9

Sulfonyl of sulfonamides as anti-diabetic agents.

Fig. 10

Sulfonyl of sulfonamides as anti-diabetic agents.

Fig. 11

Some representative sulfonyl or sulfonamides containing potential anti-inflammatory agents.

Fig. 12

Some of the representative potent sulfonyl of sulfonamides as anti-inflammatory agents.

Fig. 13

Sulfonyl of sulfonamides as anti-inflammatory agents.

Fig. 14

Sulfonyl of sulfonamides as anti-inflammatory agents.

Fig. 15

Some representative potential anti-malarial sulfonyl or sulfanamide agents.

Fig. 16

Sulfonyl of sulfonamides as anti-malarial agents.

Fig. 17

Sulfonyl of sulfonamides as anti-malarial agents.

Fig. 18

Some of the sulfonyl or sulfonamides containing heterocycles as potential Alzheimer's agents.

Fig. 19

Sulfonyl of sulfonamides as Alzheimer's agents.

Fig. 20

2D-binding mode of compound 217 within the active site of AChE.

Fig. 21

3D-binding mode of compound 217 with in the active site of AChE.

Fig. 22

Best 2D-docked pose of compound 223 within the AChE active site (PDB code: 3I6Z).

Fig. 23

Best 2D-docked pose of compound 223 within the BChE active site (PDB code: 4BDS).

Fig. 24

Best 3D-docked pose of compound 223 within (24) the AChE active site, and (25) the BChE active site. Green dashed lines represent hydrogen bond interactions. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 25

Best 3D-docked pose of compound 223 within (24) the AChE active site, and (25) the BChE active site. Green dashed lines represent hydrogen bond interactions. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 26

Sulfonyl of sulfonamides as Alzheimer's agents.

Fig. 27

Sulfonyl of sulfonamides as Antileishmanial agents.

Fig. 28

Some of the sulfonyl or sulfonamides containing heterocycles as potential TB agents.

Fig. 29

Sulfonyl or sulfonamides as potent anti-Tuberculosis agents.

Fig. 30

Sulfonyl or sulfonamides potent anti-viral agents.

Fig. 31

Sulfonyl or sulfonamides potent anti-viral agents.

Fig. 32

Sulfonyl or sulfonamides potent anti-viral agents.

Fig. 33

Sulfonyl or sulfonamides potent carbonic anhydrase agents.

Fig. 34

Sulfonyl or sulfonamides as potent Cannabinoid receptor agonists.

Fig. 35

Sulfonyl or sulfonamides as potent anticonvulsant agents.

Fig. 36

Sulfonyl or sulfonamides as potent anticancer agents.

Fig. 36

Sulfonyl or sulfonamides as potent anticancer agents.

Fig. 37

Sulfonyl or sulfonamides as potent 5-HT6 receptor.

Fig. 38

Sulfonyl or sulfonamides showed diverse biological properties.

Fig. 39

2D (left) and 3D (right) interactions of most active bTNAP inhibitor 321.

Fig. 40

Sulfonyl or sulfonamides with diverse pharmacological properties.

Fig. 41

Sulfonyl or sulfonamides showed diverse biological properties.

Fig. 42

X-ray crystal structures of PTP1B/compound complex (Fig. 42). PTP1B/5 (2B07); (Fig. 43) PTP1B/6 (2F6Z) The residues related to selectivity are labeled with black words and coloured by cyan. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 43

X-ray crystal structures of PTP1B/compound complex (Fig. 42). PTP1B/5 (2B07); (Fig. 43) PTP1B/6 (2F6Z) The residues related to selectivity are labeled with black words and coloured by cyan. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 44

Sulfonyl or sulfonamides showed diverse biological properties.

Fig. 45

2D-ligand protein interaction scheme of compound 337 (PDB code: 3EQM).