INTRODUCTION:

In continuation of our earlier work, the synthesis of 1, 8-naphthyridine based semicarbazides and amino-Oxadiazole derivatives by introducing different substituents have been published without their pharmacological profile. Our current efforts are focused in identifying the significant activities of these compounds have been reported such as antifungal activity against Alternariaalternata, Fusariumoxysporum and Curvularialunata employing the glass slide humid chamber technique using Griseofulvin as standard for comparison more compounds displayed a high order of antifungal activity. In recent scenario, heterocycles play a major role in drug synthesis. In that respect, we design and synthesize a new series of benzofuranoneoxadiazole motifs. Newer structural elements consisting of both 1,8-naphthyridine and 2-iminothiazolidin-4-ones scaffold is a centre of attention in all the nitrogen containing heterocycles due to their biological importance. Attempts were made earlier to enhance the fungi toxicity of semicarbazide and oxadozole derivatives by introducing different substituents.

A number of 1, 8-naphthyridines were equipped as probable bioactive compounds and a very wide range of biological activities are associated with this compounds.1, 8-naphthyridine compounds have been found to be effective in controlling some of the post-harvest fungal diseases. Hide and Hirst¹, Byrde and Willetts²have reported that these compounds are active against several pathogenic fungi. The 1,8-naphthyridine group of compounds have been proved to be active antibacterial^3-5. One of the 1,8-naphthyridine compound, nalidixic acid (1-ethyl-3-carboxy-7-methyl-1,8-naphthyridin-4-one) was found to be effective against gram negative bacteria of chronic urinary tract infections⁶. The antimicrobial activity⁷of 1,8-naphthyridine derivatives. In addition, a variety of pharmacological activities have also been exhibited by 2,3-disubstituted,1,8-naphthyridines, for example 2-amino-1,8-naphthyridine-3-carboxamide is well known for its diuretic⁸ property. Further, there has been growing interest in screening the 1,8-naphthyridines for their potent antibacterial and antifungal properties.

A large number of 1,8-naphthyridine derivatives are reported to exhibit antibacterial, antimalarial⁹and anticancer¹⁰activities. Our earlier studies also have shown good antifungal and antibacterial activities^11-15. The present study has been aimed at antifungal activity of newly synthesized 2-methyl-1,8-naphthyridine containing semicarbazides and amino-oxadiazole. The antifungal effect of compounds was evaluated using glass slide humid chamber technique^16,17. Their structures are mentioned below. Their antifungal activities are given in Table-1 and Table-2.

RESULTS AND DISCUSSION:

Screening for antifungal activity:

Compounds (1a-j) and (2a-j) were screened for their antifungal activity. The antifungal activity of 2-methyl-1,8-naphthyridine containing semicarbazides and amino-oxadiazolyls were screened against three fungi. Their antifungal activities are reported in Table-1 and Table-2. Perusal of Table-1 reveals that the compound 1d exhibited maximum inhibition of Alternaria alternata in its low concentration while compound 1f is more active against Curvularialunata only. The moderate activity is observed by compounds 1a, 1c, 1f and 1g against Alternaria alternate and Fusarium oxysporum. In general it is found that compounds with chlorine substituted are more toxic against the three fungi used.

Perusal of the above Table 2 reveals the antifungal activity of amino-oxadiazolyl-1,8-naphthyridines. It was evident that the compounds with chloro substituted (2d, 2f and 2g) were found to exhibit very high activity against all the fungi. Aryloxymethyl derivatives (compounds 2e, 2f and 2g) are more active when compared to the corresponding aryl substituents. Compound 1a is more toxic to Fusariumoxysporum and less toxic against Alternaria alternata and Curvularialunata. The remaining compounds 1b and 1c were least effective. In general, it was found that all the derivatives (1a-j) and (2a-j) showed the antifungal activity either at lower or higher concentrations with the variation in their activities.

All the newly synthesized compounds were screened for their antifungal activity against Alternaria alternata, Fusariumoxysporum and Curvularialunata employing the glass slide humid chamber technique. The stock solution for each of the test compounds was prepared by dissolving 10µg/ml of it in 10ml of ethyl alcohol different concentrations were obtained by diluting with distilled water. The solvents treated in a similar manner without any test compound served as control. The spore germination was so adjusted as to appear 30-40 spores per microscope field (H.P). The experiment was conducted in quadruplicate and repeated at least three times. The controls and treatments were incubated at room temperature (27±2⁰C) for 24 hours. At the end of incubation period, the numbers of spores germinated were counted to calculate the percentage of spore germination using Griseofulvin as standard.

Table 1: Antifungal screening data of N¹-(aryl/aryloxyacetyl)-N⁴-(2-methyl-1, 8-naphthyridin-3-yl) semicarbazides(1a-j).

S. No.	R	Conc.in ppm	% of germination inhibition
S. No.	R	Conc.in ppm	*A. alternata*	*F. oxysporum*	*C. lunata*
1a	-C₆H₅	30	18.55	20.50	16.55
		60	36.10	41.35	35.00
		90	51.38	63.33	60.75
1b	-C₆H₄ -CH₃	100	19.32	18.72	20.40
		150	38.62	40.12	36.12
		200	56.23	58.46	60.18
1c	-CH₂-C₆H₅	100	18.02	17.22	20.00
		150	37.02	40.02	36.02
		200	55.03	57.26	60.08
1d	-C₆H₄ -OCH₃	30	18.50	20.73	20.17
		60	37.33	40.14	38.32
		90	58.12	59.10	60.82
1e	-C₆H₄-4-Cl	30	20.00	22.50	20.15
		60	43.85	45.70	41.37
		90	70.71	68.33	75.66
1f	-CH₂OC₆H₅	100	18.15	20.14	21.02
		150	39.85	41.73	36.85
		200	57.39	62.79	70.00
1g	-CH₂OC₆H₄-4-CH₃	30	18.05	20.00	16.05
		60	36.00	41.05	34.00
		90	51.08	63.03	60.05
1h	-CH₂OC₆H₄-4-Cl	30	15.44	17.31	15.66
		60	31.75	35.66	38.75
		90	53.50	55.55	76.11
1i	-CH₂OC₆H₃-2- Cl-4-Cl	30	20.34	20.12	17.48
		60	38.09	35.78	40.06
		90	56.02	55.32	59.08
1j	CH(CH₃)OC₆H₄-4-Cl	100	18.50	20.73	20.02
		150	37.33	40.14	35.85
		200	58.12	59.10	69.00

Table 2: Antifungal screening data of 2-methyl(5-aryl/aryloxy methyl)-1,3,4-oxadiazol- 2-yl) amino-1, 8-naphthyridines (2a-j).

S. No.	R	Conc.in ppm	% of germination inhibition
S. No.	R	Conc.in ppm	*A. alternata*	*F. oxysporum*	*C. lunata*
2a	-C₆H₅	30	18.16	21.32	15.14
		60	40.12	44.18	38.14
		90	54.42	68.12	62.86
2b	-C₆H₄ -CH₃	100	20.18	19.31	20.72
		150	39.26	44.78	39.17
		200	48.74	49.63	52.36
2c	-CH₂-C₆H₅	100	17.02	16.22	19.00
		150	35.02	38.02	34.02
		200	54.03	55.26	57.08
2d	-C₆H₄ -OCH₃	100	20.50	20.10	21.92
		150	39.46	42.24	39.73
		200	60.12	51.10	52.28
2e	-C₆H₄-4-Cl	30	22.63	18.40	18.12
		60	45.36	43.70	40.73
		90	68.76	69.12	70.42
2f	-CH₂OC₆H₅	100	19.93	21.41	22.91
		150	40.75	44.32	39.76
		200	59.79	66.78	62.88
2g	-CH₂OC₆H₄-4-CH₃	30	18.85	20.90	16.55
		60	36.80	41.95	34.09
		90	51.88	63.93	60.95
2h	-CH₂OC₆H₄-4-Cl	30	17.73	17.12	14.32
		60	36.77	38.66	39.13
		90	70.85	71.14	74.74
2i	-CH₂OC₆H₃-2- Cl-4-Cl	30	20.78	22.14	18.36
		60	39.86	39.14	41.78
		90	68.76	72.55	71.22
2j	CH(CH₃)OC₆H₄-4-Cl	100	22.43	17.40	20.02
		150	44.06	41.70	35.85
		200	65.76	67.12	69.00

CONCLUSION:

All the newly synthesized compounds were screened for their antifungal activity against Alternaria alternata, fusariumoxysporum and Curvularialunata employing the glass slide humid chamber technique using Griseofulvin as standard for comparison. Compounds 1e, 2e, 2h and 2i displayed a high order of antifungal activity against all the three types of organisms used. Compounds 1d, 2d and 2f are against active A. alternata. Compounds 2a and 2j are active against F. oxysporum and compounds 1f and 1h are active against C. lunata.

ACKNOWLEDGEMENTS:

One of the authors (K.R.) is gratified to the CSIR-UGC, New Delhi, India for the award of junior research fellowship. The authors are indebted to Vice-Chancellor, Mahatma Gandhi University, Nalgonda, India for providing the research facilities and constant support.

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Received on 09.12.2020 Modified on 16.03.2021

Research J. Pharm.and Tech 2022; 15(2):757-760.

DOI: 10.52711/0974-360X.2022.00126