Utility of 5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide in the synthesis of heterocyclic compounds with antimicrobial activity

Background Pyrazolines show different biological activities. In recent years, interest in the chemistry of hydrazonoyl halides has been renewed. 1,3,4-Thiadiazoles are one of the most common heterocyclic pharmacophores with a wide range of biological activities. Results Ethyl 2-(5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-methyl-thiazole-5-carboxylate, 2-(5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one, and 1-(2-(5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-methylthiazol-5-yl)ethan-1-one were synthesized from the reaction of 5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide with different halogenated compounds. Thiazole, 1,3,4-thiadiazole and pyrano[2,3-d]thiazole derivatives were also synthesized. The structures of the newly synthesized compounds were elucidated based on elemental analysis, spectral data, and alternative synthetic routes whenever possible. Additionally, the newly synthesized compounds were screened for antimicrobial activity against various microorganisms. Conclusions A new series of novel functionalized 1,3,4-thiadiazoles, 1,3-thiazoles, and pyrazoline-containing moieties were synthesized using hydrazonoyl halides as precursors and evaluated for their in vitro antibacterial, and antifungal activities. The antimicrobial results of the examined compounds revealed promising results and some derivatives have activities similar to the references used. Electronic supplementary material The online version of this article (10.1186/s13065-019-0566-y) contains supplementary material, which is available to authorized users.


Antimicrobial activity
For their in vitro antibacterial activity against Streptococcus pneumonia and Bacillus subtilis and Pseudomonas aeruginosa and Escherichia coli, twenty-one of the newly synthesized target compounds were assessed. They were also assessed against a representative panel of fungal strains for their in vitro antifungal activity (i.e., Aspergillus fumigatus and Candida albicans). Ampicillin and gentamicin for in vitro antibacterial activity were used as reference drugs; While Amphotericin B was used for in vitro antifungal activity as a reference drug. Examinations were conducted at Al-Azhar University's Regional Center for Mycology and Biotechnology (Nasr City, Cairo, Egypt). Microbes were obtained from the Microbiological Resource Center, Faculty of Agriculture, Ain Shams University, Cairo, Egypt. According to these results, we can suggest the following structure activity relationships: A. In the thiazoles (3), (4), and (14) (1) Attachment of C 10 H 7 OCO group in (14) at position 5 in the thiazole ring is very important for antimicrobial activity and increases the activity towards Gram-negative bact. (2) Attachment of H or CH 3 CO group at position 5 in the thiazole ring showed a moderate antimicrobial activity for all microorganisms in Table 1.
C. In the thiazolylpyrazoles 10, 11(a-b) (1) Attachment of methyl and -N=NPh groups in (10a) and attachment of OH and -N=NPh groups in (11b) at positions 3, 4 respectively, in the moiety of the pyrazole ring had no activity against all the tested Gram-positive and Gramnegative bact. but had moderate activity against test fungi. D. In the thiazolylquinazolinedione (13) (1) Attachment of quinazoline-2,4(1H,3H)-dione ring at position 5 in the thiazole ring showed a moderate antimicrobial activity for all microorganisms in Table 1.
E. In the thiazolyloxadiazole (15) (1) Attachment of 1,3,4-oxadiazole-2-thiole ring at position 5 in the thiazole ring showed a moderate antimicrobial activity for all microorganisms in Table 1.  F. In the thiazolylthiadiazole carbohydrazide (20a-d) (1) Attachment of C 2 H 5 CO 2 group in (20a) at position 2 in the moiety of the 1,3,4-thiadiazole ring displayed potent effect against Af fungus, moderate activity against Gram-positive bact., Gram-negative bact., and CA fungus. (1) Attachment of CH 3 -group in (21a) at position 4 in the moiety of the thiazole ring displayed a moderate antimicrobial activity for all microorganisms in Table 1. (2) Attachment of C 6 H 5 -group in (21b) at position 4 in the moiety of the thiazole ring displayed a moderate antimicrobial activity for all microorganisms in Table 1 except PA which has no activity.
(1) Attachment of C 6 H 5 -group in (25a) at position 7 in the moiety of the pyrano[2,3-d]thiazole-6-carbonitrile ring displayed a moderate antimicrobial activity for all microorganisms in Table 1.

Conclusions
Hydrazonoyl halides were used as precursors to synthesize a new series of novel functionalized 1,3,4-thiadiazoles, 1,3-thiazoles and pyrazoline-containing moieties. Antibacterial and antifungal activities of these compounds were assessed in vitro.
The reaction mixture was left to cool to room temperature. The formed solid was filtered off, dried, and recrystallized from an appropriate solvent to obtain the corresponding compounds (2-4), respectively.